On December 6, 2017 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported results from the positive, pivotal Phase III IMpower150 study of Tecentriq (atezolizumab) and Avastin (bevacizumab) plus chemotherapy (carboplatin and paclitaxel) in people with previously untreated advanced non-squamous non-small cell lung cancer (NSCLC) (Press release, Hoffmann-La Roche, DEC 6, 2017, View Source [SID1234522415]). The study showed that people who received Tecentriq and Avastin plus chemotherapy had a 38 percent reduced risk of their disease worsening or death (progression-free survival, PFS) compared with those who received Avastin plus chemotherapy (hazard ratio [HR]=0.62; p<0.0001 95 % CI: 0.52-0.74; median PFS = 8.3 vs. 6.8 months). Importantly, a doubling of the 12-month landmark PFS rate was observed with the combination of Tecentriq and Avastin plus chemotherapy (37 percent) compared to Avastin plus chemotherapy (18 percent). The rate of tumour shrinkage (overall response rate, ORR), a secondary endpoint in the study, was higher in people treated with Tecentriq and Avastin plus chemotherapy compared with Avastin plus chemotherapy (64 percent vs. 48 percent). The safety profile of the Tecentriq and Avastin plus chemotherapy combination was consistent with the safety profiles of the individual medicines, and no new safety signals were identified with the combination.

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The 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, ITT-WT) and in a subgroup of people who had a specific biomarker (T-effector "Teff" gene signature expression Teff WT). IMpower150 met its PFS co-primary endpoint per study protocol for both populations assessed. In the Teff-WT population, the combination of Tecentriq and Avastin plus chemotherapy reduced the risk of disease worsening or death by 49 percent compared to Avastin plus chemotherapy (HR=0.51; p<0.0001 95% CI: 0.38-0.68; median PFS = 11.3 vs 6.8 months).
"This Tecentriq study is the first positive Phase III combination trial that showed a cancer immunotherapy reduced the risk of the disease getting worse when used as an initial treatment in a broad group of people with advanced non-squamous NSCLC," Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "The IMpower150 study represents an important advance in lung cancer treatment, and we will submit these results to regulatory authorities around the world to potentially bring a new standard of care to people living with this disease as soon as possible."

The late-breaking IMpower150 data will be presented at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Immuno Oncology Congress (Abstract #LBA1_PR) on Thursday, 7 December 6.15 pm. Central European Time (CET) and are also part of the official press programme. Early results from the co-primary endpoint of overall survival (OS) are encouraging. While they are not yet fully mature, these preliminary OS results will be presented at the ESMO (Free ESMO Whitepaper) IO congress. The next analysis of survival is expected in the first half of 2018.

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 or recurrent metastatic 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.

Due to pre-specified statistical testing hierarchy, Arm A vs Arm C has not been formally tested yet. IMpower150 was designed to formally compare Tecentriq plus chemotherapy (Arm A) versus Avastin plus chemotherapy (Arm C), only if Tecentriq and Avastin plus chemotherapy (Arm B) is shown to improve OS in the ITT-WT population compared to Avastin plus chemotherapy (Arm C). These OS results are expected in the first half of 2018.

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.

A summary of the IMpower150 Arm B vs Arm C PFS and ORR results are included below; additional data, including preliminary OS results and Arm A vs Arm C PFS will be presented as part of the Late-Breaking Abstract presentation.

The safety profile of Tecentriq and Avastin plus chemotherapy combination was consistent with the safety profiles of the individual medicines, and no new safety signals were identified with the combination. Serious adverse events related to treatment were observed in 25.4 percent of people who received Tecentriq and Avastin plus chemotherapy compared to 19.3 percent of those who received Avastin plus chemotherapy.

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 globally1. 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 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.

On December 6, 2017 Ayala Pharmaceuticals, a biopharmaceutical company dedicated to developing targeted cancer therapies, reported that they have entered into an exclusive worldwide license agreement with Bristol-Myers Squibb for two gamma secretase inhibitors in development for the treatment of cancers with altered Notch genes (Press release, Ayala Pharmaceuticals, DEC 6, 2017, View Source [SID1234522417]).

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Under the terms of the license agreement, Ayala will have exclusive worldwide development and commercialization rights for BMS-906024 and BMS-986115, two gamma secretase inhibitors previously developed by BMS as a Notch inhibitor for oncology indications. In connection with the license, BMS received an upfront payment, became a shareholder of Ayala, and is eligible to receive certain development, regulatory, and sales-based milestones, as well as tiered annual net sales royalties. Ayala is responsible for all future development and commercialization of BMS-906024 and BMS-986115.

Israel Biotech Fund identified the opportunity, led the due diligence and syndicated with aMoon and Harel Insurance in 2017 to form Ayala. The new company intends to develop BMS-906024 as a precision medicine for niche orphan patient populations harboring Notch activating mutations.

"We believe BMS-906024 is the best in class gamma secretase inhibitor," said Ayala’s Chairman of the Board of Directors, David Sidransky, MD. "Although most Notch targeted clinical trials have traditionally recruited non-selected populations, our approach is to target patients with specific Notch alterations whose tumors are expected to respond directly to this treatment." Dr. Sidransky is a Co-Founder and Managing Partner of Israel Biotech Fund. He was Vice Chairman of ImClone Systems until its acquisition by Eli Lilly and the chairman and board member of several NASDAQ listed biotech companies.

"This is an exciting opportunity in personalized therapy for Oncology, bringing new hope to cancer patients with no approved treatment options," said Roni Mamluk, PhD, CEO at Ayala. "We plan to initiate phase 2 clinical trials in 2018." Roni Mamluk, is the former CEO of Chiasma and a member of its board of directors.

"Partnering with Ayala allows for the continued development of BMS-906024 and BMS-986115 and demonstrates our commitment to seeking opportunities that enable the continued development of drug candidates that might benefit certain patients," said Tim Reilly, Vice President, Head of Early Oncology Development at BMS. "Dr. Sidransky and Ayala are strategically positioned to focus their resources on the targeted development of these candidates for the treatment of cancers with altered Notch genes."

On December 6, 2017 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the U.S. Food and Drug Administration (FDA) has granted full approval for Avastin (bevacizumab) for the treatment of adults with glioblastoma that progressed following prior therapy (referred to as recurrent disease) (Press release, Hoffmann-La Roche, DEC 6, 2017, View Source [SID1234522404]). Avastin was previously granted provisional approval in this setting under the FDA’s accelerated approval program.

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"Glioblastoma is the most common and aggressive form of brain cancer and can be very difficult to treat," said Sandra Horning, M.D., chief medical officer and head of Global Product Development. "Delaying disease progression and reducing the need for corticosteroids over the course of treatment are considered important goals for those impacted by this devastating disease where patients have limited treatment options."
This conversion to full approval was based on the totality of evidence of Avastin in glioblastoma, including data from the Phase III EORTC 26101 study. Avastin is now approved in the United States for nine distinct uses across six different types of cancer.

About the EORTC 26101 Study

EORTC 26101 is an independent Phase III, multicenter, randomized, open-label trial, conducted by the European Organization for Research and Treatment of Cancer (EORTC), which evaluated the addition of Avastin to lomustine chemotherapy in 432 patients with previously treated glioblastoma. The primary endpoint of the study was overall survival (OS), and progression-free survival (PFS) as assessed by investigator and overall response rate (ORR) were key secondary endpoints. Results showed the following:

There was no significant increase in OS with Avastin-based treatment (HR=0.91, p=0.4578).
As the primary endpoint was not met, all secondary endpoints should be considered descriptive only.

Avastin-based treatment increased the time to disease progression or death compared to chemotherapy alone (median PFS: 4.2 months vs. 1.5 months, HR=0.52, 95% CI: 0.41-0.64).

Among people taking corticosteroids at baseline (50 percent), more people were able to completely stop intake of corticosteroids while on treatment in the Avastin arm compared to the control arm (23 percent vs. 12 percent).

In the Avastin with lomustine arm, 22 percent of people discontinued treatment due to adverse reactions compared with 10 percent of people in the lomustine arm.

Adverse events were consistent with those seen in previous trials of Avastin across tumor types for approved indications.

About Glioblastoma

Glioma (cancer of the glial cells) is the most common type of malignant primary brain tumor (a tumor that originates in the brain), and represents nearly one-fourth of all primary brain tumors and three-fourths of all malignant tumors1. Glioblastoma (or glioblastoma multiforme) is the most common and the most aggressive type of glioma, accounting for more than half of all gliomas. It is estimated that more than 12,300 people will be diagnosed with glioblastoma in the United States in 20171.

About Avastin

With the initial approval in the United States for advanced colorectal cancer in 2004, Avastin became the first anti-angiogenic therapy made widely available for the treatment of patients with an advanced cancer.

Today, Avastin is continuing to transform cancer care through its proven survival benefit (overall survival and/or progression free survival) across several types of cancer. Avastin is approved in Europe for the treatment of advanced stages of breast cancer, colorectal cancer, non-small cell lung cancer, kidney cancer, ovarian cancer and cervical cancer, and is available in the United States for the treatment of colorectal cancer, non-small cell lung cancer, kidney cancer, cervical cancer and recurrent, platinum-resistant and platinum-sensitive ovarian cancer. In addition, Avastin is approved over 70 other countries worldwide for the treatment of patients with progressive glioblastoma following prior therapy. Avastin is approved in Japan for the treatment of the advanced stages of colorectal cancer, non-small cell lung cancer, cervical cancer, breast cancer, ovarian cancer and malignant glioma, including newly diagnosed glioblastoma.

Avastin has made anti-angiogenic therapy a fundamental pillar of cancer treatment today. Over 2.7 million patients have been treated with Avastin so far. A comprehensive clinical programme with more than 300 ongoing clinical trials is investigating the use of Avastin in over 50 tumour types.

On December 6, 2017 Prometic Life Sciences Inc. (TSX: PLI) (OTCQX: PFSCF) (Prometic) reported that it will have two presentations at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting being held Dec. 9-12, 2017 in Atlanta (Press release, ProMetic Life Sciences, DEC 6, 2017, View Source [SID1234522398]).

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An oral presentation, entitled, "Pivotal Trial with Intravenous Plasminogen Replacement in Patients with Plasminogen Deficiency Demonstrates Long-Term Efficacy for Treatment and Prevention of Ligneous Lesions" will be presented by Dr. Charles T. Nakar, Indiana Hemophilia and Thrombosis Center. During the oral session, Dr. Nakar will present 48-week data demonstrating the long-term safety and efficacy of intravenous plasminogen replacement (RyplazimTM) in patients with plasminogen deficiency.

A poster presentation, entitled, "Computer Modeling Using Historical Data Demonstrates a Significant Reduction in Expected Extravascular Fibrinous Lesions Due to Congenital Plasminogen Deficiency While Receiving Intravenous Plasminogen Replacement" will be presented by Dr. Joseph M. Parker, Senior Director of clinical development of Prometic. Dr. Parker will present a poster of historical data computer modeling highlighting the significant treatment effect of RyplazimTM in reducing the extravascular ligneous lesions in pediatric and adult subjects with plasminogen deficiency.

"Data from these presentations demonstrates the remarkable safety and efficacy profile of plasminogen treatment we have observed to date," said Pierre Laurin, Chief Executive Officer at Prometic. "No currently-available treatment options have demonstrated a complete resolution of lesions in patients with plasminogen deficiency. We are continuing to work closely with the FDA with the goal of making our plasminogen replacement therapy available to patients as soon as possible."

Details of the oral presentation are as follows:

Presentation Title: Pivotal Trial with Intravenous Plasminogen Replacement in Patients with Plasminogen Deficiency Demonstrates Long-Term Efficacy for Treatment and Prevention of Ligneous Lesions

Presenter: Charles T. Nakar, M.D.

Session Title: Disorders of Coagulation or Fibrinolysis: Novel Therapies and Clinical Trials in Bleeding Disorders
Date/Time: Saturday, December 9, 2017 at 9:30 a.m. EST
Room: Georgia World Congress Center, Bldg B, Lvl 2, B207-B208

Details of the poster presentation are as follows:

Presentation Title: Computer Modeling Using Historical Data Demonstrates a Significant Reduction in Expected Extravascular Fibrinous Lesions Due to Congenital Plasminogen Deficiency While Receiving Intravenous Plasminogen (PLG) Replacement

Presenter: Joseph M. Parker, M.D.
Session Title: Disorders of Coagulation or Fibrinolysis: Poster II
Date/Time: Sunday, December 10, 2017 from 6:00 p.m. to 8:00 p.m. EST
Room: Georgia World Congress Center, Bldg A, Lvl 1, Hall A2

On December 6, 2017 Synaffix BV, a biotechnology company that has developed a proprietary site-specific conjugation platform technology to enable differentiated antibody-drug conjugates (ADCs), reported the launch of a new platform of highly potent cytotoxic ADC payloads that will­­ be integrated into its existing ADC platform (Press release, Synaffix, DEC 6, 2017, View Source [SID1234522419]). With this expansion, Synaffix becomes a one-stop provider for technologies required to rapidly translate antibodies into proprietary ADC products.

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The new toxSYN platform consists of four highly potent payloads, which offer multiple mechanisms of action and a viable path for commercialization when combined with the components of the company’s GlycoConnect and HydraSpace technologies:

Syneamicin functionalized calicheamicin (DNA damaging agent)
SYN-38 functionalized SN-38 (topoisomerase 2 inhibitor)
Synstatin E functionalized auristatin E (microtubule inhibitor)
Syntansine functionalized maytansine (microtubule inhibitor)
All the payloads have been clinically validated with well-known efficacy and safety profiles, and were selected to address the two types of biologies that exist across ADC targets which include rapidly-dividing cancer cells as well as quiescent cells, such as cancer stem cells.

"We expect this important expansion of our ADC technology to further advance our internal research and facilitate collaborations with a much broader set of companies" said Peter van de Sande, CEO of Synaffix. "By providing these four distinct payloads through our new toxSYN platform, we can now enable any company with an existing antibody to rapidly establish a highly-competitive clinical-stage ADC program for its own development pipeline."

About Synaffix Site-Specific ADC Platform Technology

The growing experience of Synaffix and its collaboration partners continues to confirm the ability of our conjugation platform technology to consistently generate ADCs that are more effective and better tolerated when compared to all three major clinical-stage ADC conjugation technologies. The proprietary conjugation technology platform of Synaffix is comprised of GlycoConnect, the site-specific and stable antibody conjugation technology that involves proprietary enzymes and metal-free click conjugation components, and HydraSpace, the highly polar ADC-enhancing spacer technology.

GlycoConnect was shown to be capable of significantly enhancing the therapeutic index of an ADC on its own. The highly polar properties of HydraSpace improve the solubility and stability of the payload and the resulting ADC product, thus enhancing further the therapeutic index of the ADC.

Both technologies have demonstrated compatibility with all ADC payload classes and all IgG isotypes and can be applied directly to an existing antibody without any DNA and or protein engineering.