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 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.

On December 6, 2017 Foundation Medicine, Inc. (NASDAQ:FMI) reported that new data generated with FoundationOneHeme, its comprehensive genomic profiling (CGP) assay for hematologic malignancies and sarcomas, will be presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, Foundation Medicine, DEC 6, 2017, View Source [SID1234522397]). Data from a broad range of blood cancers, including acute myeloid leukemia (AML), myeloproliferative neoplasms (MPN), and non-Hodgkin lymphoma (NHL), including primary central nervous system lymphoma (PCL), demonstrate the value of integrating FoundationOneHeme into clinical care. The data presented is expected to demonstrate the potential for CGP to improve disease classification, to offer personalized prognostic information and to support therapeutic treatment decision making by informing treating physicians about the use of novel treatment options, including cancer immunotherapies.

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"Comprehensive genomic profiling (CGP) is proving to be an essential component for personalized cancer care, particularly as we learn more about the diverse genomic alterations in blood cancers," said Vincent Miller, M.D., chief medical officer at Foundation Medicine. "FoundationOneHeme is at the forefront of helping to identify new treatment approaches, including cancer immunotherapy, for individuals with blood cancers. Our new findings to be presented at ASH (Free ASH Whitepaper) support the ability of CGP to address high unmet medical needs across a wide range of hematologic malignancies, including rare conditions for which there are few treatment options."

Cancer immunotherapy is emerging as a therapeutic tool for patients with diverse hematologic malignancies. New results to be presented at ASH (Free ASH Whitepaper) using FoundationOneHeme show that more than one-quarter of patients with PCL had high tumor mutational burden (TMB), a genomic biomarker that has been shown across several cancer types to predict response to immuno-oncology treatment strategies, such as checkpoint inhibitors. Less than 50 percent of PCL patients achieve complete remission with current standard of care treatments, underscoring a need for new treatment options for these patients.

New results also support the role of FoundationOneHeme to guide therapy selection and predict response to treatment. In an oral study to be presented, FoundationOneHeme detected NTRK fusions in a wide variety of hematologic malignancies, and clinical response to a TRK inhibitor was subsequently observed in a patient with refractory AML and an ETV6-NTRK2 fusion. In another study to be presented, CGP offered insights that may facilitate risk-adapted clinical management decisions in patients with intermediate-and favorable-risk AML, potentially informing optimal use of autologous stem cell transplantation (auto-SCT) over conventional consolidation chemotherapy. For example, the study showed the presence of PTPN11 mutations to predict long term clinical outcomes following an auto-SCT.

Other results to be presented at ASH (Free ASH Whitepaper) demonstrate the ability of FoundationOneHeme to detect both known and novel BCL6 rearrangements in NHL, including cases that previously tested negative with standard-of-care single marker testing. BCL6 rearrangements have known diagnostic and prognostic utility in specific subtypes of NHL.

Foundation Medicine and collaborators will present a total of nine studies, including four oral presentations and five poster presentations, at the ASH (Free ASH Whitepaper) Annual Meeting from December 9-12, 2017 in Atlanta. The planned presentations are as follows:

Dec 9:

115 – Unrecognized clonal hematopoiesis of indeterminate potential in solid tumors: Implications for interpretation of molecular testing, Dec 9, 9:30am, C208-210 (Oral Presentation)
1423 – The role of comprehensive mutational profiling in predicting patients who may benefit from autologous hematopoietic cell transplant for acute myeloid leukemia, Dec 9, 5:30pm-7:30pm, Hall A2 (Poster Presentation)
1657 – A distinct mutation profile might contribute to the dismal outcome of triple negative patients with primary myelofibrosis, Dec 9, 5:30pm-7:30pm, Hall A2 (Poster Presentation)
Dec 10:

417 – Comprehensive genomic profiling identifies novel BCL6 rearrangements in diverse subtypes of Non-Hodgkin lymphoma as well as known rearrangements not detected using standard of care assays, Dec 10, 12:30pm, Marcus Auditorium (Oral Presentation)
476 – Comprehensive genomic profiling identifies genomic alterations that define Philadelphia-like B-acute lymphoblastic leukemia, Dec 10, 4:45pm, B213-B214 (Oral Presentation)
Dec 11:

794 – Characterization of NTRK fusions and therapeutic response to NTRK inhibition in hematologic malignancies, Dec 11, 4:45pm, B207-208 (Oral Presentation)
3800 – Recurrent copy number variants are highly prevalent in acute myeloid leukemia, Dec 11, 6:00pm-8:00pm, Hall A2 (Poster Presentation)
3996 – Comprehensive genomic profiling demonstrates differences in primary CNS lymphoma and systemic diffuse large B cell lymphoma and reveals biomarkers indicating potential benefit from immune checkpoint inhibitors, Dec 11, 6:00pm-8:00pm, Hall A2 (Poster Presentation)
4016 – Next generation sequencing of Castleman disease and follicular dendritic cell sarcomas associated with Castleman disease, Dec 11, 6:00pm-8:00pm, Hall A2 (Poster Presentation)

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.