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 Sirnaomics, Inc. (www.sirnaomics.com), a leading biopharmaceutical company in discovery and development of RNAi therapeutics, reported that the Office of Orphan Product Development division of the FDA has granted Orphan-drug designation to its leading therapeutic candidate, STP705, for the treatment of Cholangiocarcinoma (CCA) (Press release, Sirnaomics, DEC 6, 2017, View Source [SID1234523487]).

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Sirnaomics lead product candidate, STP705, is an siRNA (small interfering RNA) therapeutic which takes advantage of a dual-targeted inhibitory property and polypeptide nanoparticle (PNP)-enhanced delivery to directly knock down both TGF-β1 and COX-2 gene expression. The product has also received both US FDA and Chinese FDA IND approval for Hypertrophic Scar Reduction and it is expected to have efficacy in many diseases across multiple therapeutic areas. The Orphan Drug application was supported by recent results of in vitro and in vivo studies using a human cholangiocarcinoma cell line and its xenograft tumor in a mouse model.

"We are very pleased to reach this significant milestone and we are very excited to develop our lead product candidate for this oncology indication," stated Dr. Patrick Lu, founder and CEO. "This is the fourth major clinical milestone we have achieved in the past twelve months including our FDA and CFDA IND approval for STP705 for the treatment of Hypertrophic scar as well as our Orphan Drug Designation approval for Primary Sclerosing Cholangitis. The antifibrotic and antitumorigenic properties of STP705 may bring an alternative therapeutic approach for treatment of devastating cancers such as cholangiocarcinoma and others."

"The Orphan designation for CCA is a very important step for Sirnaomics and the positive data allows us to develop STP705 in a devastating oncology disease with no effective therapy," stated Dr. Michael Molyneaux, Sirnaomics’ CMO. "This Orphan designation aligns with our mission to alleviate human suffering and target diseases with high unmet clinical need and we anticipate filing an IND for CCA sometime in the first half of 2018."

On December 6, 2017 H3 Biomedicine Inc., a clinical stage biopharmaceutical company specializing in the discovery and development of precision medicines for oncology and a member of Eisai’s global Oncology Business Group, reported that company scientists are presenting data from preclinical studies involving H3B-6545, an oral, selective small molecule covalent antagonist of wild-type and mutant Estrogen Receptor (ERα) at the 40th Annual San Antonio Breast Cancer Symposium (SABCS) in San Antonio, TX (Press release, H3 Biomedicine, DEC 6, 2017, View Source [SID1234522434]). The data will be shared in a poster presentation.

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The poster, presented by Manav Korpal, Ph.D., is titled "Development of a first-in-class oral selective ERα covalent antagonist (SERCA) for the treatment of ERαWT and ERαMUT breast cancer" and is taking place in the following session:

Session: Poster Session 1: Treatment: New Drugs and Treatment Strategies (5:00 PM – 7:00 PM)
Date/Time: Wednesday, December 6, 2017, 5:00 PM
Room: Hall 1

"We are encouraged by the initial results that H3B-6545 demonstrated over the current standard of care agents in preclinical models," said Markus Warmuth, M.D., President and CEO, H3 Biomedicines. "At H3, our research in breast cancer seeks to advance the understanding of this debilitating illness and work towards discovering novel treatments for those affected by the disease."

The poster presented at SABCS demonstrated that H3B-6545 has a unique mode of ERα antagonism and exhibits superior preclinical anti-tumor activity to fulvestrant in the MCF-7 xenograft model with once daily oral dosing, achieving maximal antitumor activity at doses >10x below the maximum tolerated dose in mice. In addition, H3B-6545 demonstrated superior preclinical anti-tumor activity to both tamoxifen and fulvestrant in patient derived xenograft models of breast cancer carrying estrogen receptor mutations. Based on these results, in September, 2017, H3B-6545 entered into a Phase 1 multi-center, open-label study to evaluate the safety, pharmacokinetics, pharmacodynamics and clinical activity of the compound in women with ER-positive, Her2-negative metastatic breast cancer. Please refer to www.clinicaltrials.gov for additional clinical trial information.

"The results from the preclinical models indicate a new mode of inhibition, covalent antagonism of ERα, is potent in in vitro and in vivo models of breast cancer," said Pete Smith, Ph.D., Chief Scientific Officer, H3 Biomedicine. "The fact that current ER-directed therapies are only partially effective in the ERα mutant setting, and that a significant proportion of resistant breast cancer metastases continue to remain dependent on ERα signaling for growth/survival, highlights the critical need to develop the next generation of ERα antagonists that can overcome aberrant ERα activity."

About H3B-6545

H3B-6545 is an orally bioavailable, potent and selective small molecule modulator of wild-type and mutant Estrogen Receptor (ERα). Scientists at H3 Biomedicine have discovered a new class of ERα antagonists called Selective Estrogen Receptor Covalent Antagonists (SERCAs) that inactivate the estrogen receptor by targeting a cysteine that is not present in other nuclear hormone receptors. SERCAs have a unique biological and activity profile compared to Selective Estrogen Receptor Modulators (SERMs) and Selective Estrogen Receptor Degraders (SERDs). Preclinical data indicates H3B-6545 inhibits the growth of cell line and patient-derived xenograft models of wild-type and mutant ERα with improved activity over standard-of-care therapies. Initial clinical development will target breast cancer patients with wild-type and mutant ERα and will assess the safety, pharmacokinetics, pharmacodynamics and preliminary efficacy of H3B-6545.

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.

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."