On December 7, 2020 Guardant Health, Inc. (Nasdaq: GH), a leading precision oncology company, reported that it shares new data at the 2020 Virtual San Antonio Breast Cancer Symposium (SABCS) showing how its GuardantINFORM real-world clinical-genomic platform can be used to gain deeper insights into patients’ treatments and associated response to support the development of more effective therapies for biomarker-defined cancers (Press release, Guardant Health, DEC 7, 2020, businesswire.com/news/home/20201207005087/en/Guardant-Health-Presents-Data-at-San-Antonio-Breast-Cancer-Symposium-Demonstrating-Utility-of-GuardantINFORM-Real-World-Platform-in-Metastatic-Breast-Cancer [SID1234572368]). The data presented highlight treatment resistance in estrogen receptor positive (ER-positive), HER-2 negative metastatic breast cancer patients.

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"While we’ve seen improved outcomes for patients with ER-positive metastatic breast cancer, many eventually develop ESR1 resistance after undergoing endocrine therapy; and new data from patients treated with CDK4/6 inhibitors suggest that clinical outcomes are impacted by a patient’s molecular subtype," said Helmy Eltoukhy, Guardant Health CEO. "The results presented during SABCS demonstrate the power of our GuardantINFORM platform to deliver real-world clinical-genomic insights to help guide more precise oncology treatments and accelerate drug development efforts for these difficult to treat breast cancers."

The abstracts, now online, show how this robust platform helps characterize molecular tumor evolution and treatment resistance mechanisms throughout each patient’s treatment journey.

Abstract PS18-15: "Real-world clinical-genomic data identifies the ESR1 clonal and subclonal circulating tumor DNA (ctDNA) landscape and provides insight into clinical outcomes" shows how the data from our Guardant360 liquid biopsy dataset demonstrate the heterogeneity of ESR1 mutations associated with endocrine therapy treatment.
Abstract PS18-28: "Genomic heterogeneity and associated clinical outcomes of breast cancers treated with CDK4/6 inhibitors: Insights from real-world clinical genomic data" suggests new potential mechanisms of acquired resistance.
Abstract OT-07-01: "Guardant360 related clinical outcomes in patients who share medical records-breast cancer (GRECO-B)" shows how Guardant Health takes a novel patient-centric approach to enrolling Guardant360 breast cancer patients into this siteless, prospective, observational health outcomes study to create a more comprehensive view of patients’ clinical journey.
The GuardantINFORM platform is an in silico platform that combines de-identified longitudinal clinical information and genomic data collected from our Guardant360 liquid biopsy test. With data from over 135,000 patients, this real-world clinical-genomic dataset of advanced cancer patients is one of the largest in oncology. Notable applications include targeted drug development, clinical trial optimization, and post-marketing studies.

On December 7, 2020 Synthekine Inc., an engineered cytokine therapeutics company, reported in vivo data presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting showing STK-009, its orthogonal IL-2 ligand, improved the efficacy and durability of SYNCAR-001, its CD-19 targeted CAR-T cell therapy modified with an orthogonal IL-2 receptor (Press release, Synthekine, DEC 7, 2020, View Source [SID1234572367]). The data were delivered in a poster presentation by Paul-Joseph Aspuria, Ph.D., of Synthekine.

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"While CAR-T therapies have proven to be very effective in treating hematological malignancies, the lack of sustained activity and CAR-T cell persistence limits their full therapeutic potential in lymphoma," said Martin Oft, M.D., chief development officer at Synthekine. "The presented data demonstrate our orthogonal IL-2 system is well positioned to overcome these shortcomings. STK-009 demonstrates the ability to expand CAR-Ts in vivo in pre-clinical models, allowing for a lower starting dose of CARs while achieving deep and durable efficacy with the possibility to re-expand resting CARs long after initial transfer. We look forward to advancing STK-009 and SYNCAR-001 and filing an IND for the program in 2021."

In both disseminated and subcutaneous RAJI lymphoma models in mice evaluating the efficacy of STK-009 with SYNCAR-001, STK-009 dosing drove increased levels of circulating SYNCAR-001 cells, resulting in complete responses. STK-009 expanded both CAR-T effector cells and stem cell memory cells, resulting in deep initial responses and long-term immune surveillance. Data on STK-009 from a multiple-ascending dose study in non-human primates were also presented, showing STK-009 was well tolerated, had long exposure, and had no effect on cells expressing only the wild type IL-2 receptor. A copy of the poster is available on Synthekine’s website.

"Selectivity of this orthogonal IL-2 ligand is fundamental, as more promiscuous activity on bystander cells could lead to systemic toxicity and limit the therapeutic potential of this combined treatment," said Dr. Aspuria. "Based on the data we presented, we are optimistic about the potential for STK-009 and SYNCAR-001 to overcome hurdles faced by CD-19 cell therapy today."

On December 7, 2020 NANOBIOTIX (Paris:NANO) (Euronext: NANO – ISIN : FR0011341205 – the "Company"), a clinical-stage nanomedicine company pioneering new approaches to the treatment of cancer, reported the start of its roadshow in connection with its intention to issue and sell, subject to market and other conditions, 6,500,000 ordinary shares of the Company in an initial public offering of American Depositary Shares ("ADSs"), each representing one ordinary share, in the United States (the "U.S. Offering") and a concurrent offering of ordinary shares in certain jurisdictions outside of the United States (the "European Offering" and, together with the U.S. Offering, the "Global Offering") (Press release, Nanobiotix, DEC 7, 2020, View Source [SID1234572365]). The Company intends to grant the underwriters for the Global Offering (the "Underwriters") a 30-day option to purchase additional ADSs and/or ordinary shares in an aggregate amount of up to 15% of the total number of ADSs and ordinary shares proposed to be sold in the Global Offering.

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All securities to be sold in the Global Offering will be offered by the Company. The Company has applied to list its ADSs on the Nasdaq Global Market under the ticker symbol "NBTX." The Company’s ordinary shares are listed on the regulated market of Euronext in Paris under the symbol "NANO."

Jefferies LLC is acting as global coordinator and joint book-running manager for the Global Offering, and Evercore Group, L.L.C. and UBS Securities LLC are acting as joint book-running managers for the U.S. Offering. Jefferies International Limited and Gilbert Dupont are acting as managers for the European Offering.

The offering price per ADS in U.S. dollars and the corresponding offering price per ordinary share in euros, as well as the final number of ADSs and ordinary shares sold in the Global Offering, will be determined following a bookbuilding process.

The ADSs and/or ordinary shares will be issued through a capital increase without shareholders’ preferential subscription rights by way of a public offering excluding offerings referred to in Article L. 411-2 1° of the French Monetary and Financial Code (Code monétaire et financier) and under the provisions of Article L.225-136 of the French Commercial Code (Code de commerce) and pursuant to the 2nd and 7th resolutions of the Company’s extraordinary general shareholders’ meeting held on November 30, 2020.

The European Offering will be open only to qualified investors as such term is defined in article 2(e) of the regulation (EU) 2017/1129 of the European Parliament and of the Council of June 14, 2017.

The securities referred to in this press release will be offered only by means of a prospectus. When available, copies of the preliminary prospectus relating to and describing the terms of the Global Offering may be obtained from Jefferies LLC, 520 Madison Avenue New York, NY 10022, or by telephone at 877-547-6340 or 877-821-7388, or by email at [email protected]; or from Evercore Group L.L.C., Attention: Equity Capital Markets, 55 East 52nd Street, 35th Floor, New York, New York 10055, or by telephone at 888-474-0200, or by email at [email protected]; or from UBS Securities LLC, Attention: Prospectus Department, 1285 Avenue of the Americas, New York, New York 10019, or by telephone at 888-827-7275, or by email at [email protected].

A registration statement on Form F-1 relating to the securities referred to herein has been filed with the U.S. Securities and Exchange Commission ("SEC") but has not yet become effective. These securities may not be sold, nor may offers to buy be accepted, prior to the time the registration statement becomes effective. The registration statement can be accessed by the public on the website of the SEC.

Application will be made to list the new ordinary shares to be issued pursuant to the Global Offering on the regulated market of Euronext in Paris pursuant to a listing prospectus subject to an approval from the French Autorité des marchés financiers ("AMF") and comprising the 2019 Universal Registration Document (Document d’Enregistrement Universel) of the Company approved by the AMF on May 12, 2020 under number R. 20-010, as amended by its amendment filed with the AMF on November 20, 2020 under number D.20-0339-A01 and a Securities Note (Note d’opération), including a summary of the prospectus. Copies of the 2019 Universal Registration Document and its amendment are available free of charge at the Company’s head office located at 60, rue de Wattignies, 75012 Paris, France, on the Company’s website (www.nanobiotix.com) and on the website of the AMF (www.amf-france.org).

This press release does not constitute an offer to sell or the solicitation of an offer to buy securities in any jurisdiction, and shall not constitute an offer, solicitation or sale in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of that jurisdiction.

On December 7, 2020 Pfizer Inc. (NYSE:PFE) reported safety and clinical response results from the ongoing Phase 1 study (NCT03269136) for PF-06863135, an investigational B-cell maturation antigen (BCMA) CD3-targeted bispecific antibody (Press release, Pfizer, DEC 7, 2020, View Source [SID1234572364]). Data from 30 patients with relapsed or refractory multiple myeloma showed manageable safety across all subcutaneous dose levels with no dose-limiting toxicities observed, and 83% of patients achieved a clinical response at the highest dose level. The results will be presented today at the Virtual American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition.

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"Despite treatment advances, multiple myeloma remains incurable and there is a substantial need for breakthroughs for patients," said Jeff Settleman, Senior Vice President & Chief Scientific Officer, Oncology R&D, Pfizer. "The very high response rate observed with PF-06863135, coupled with manageable safety and the convenience of subcutaneous administration, underscores the potential impact this medicine may have for people living with this devastating disease. These findings support continued development of PF-06863135 for people with multiple myeloma, both as monotherapy and in combination with standard or novel therapies."

PF-06863135 is a bispecific antibody designed to bind to BCMA which is highly expressed on the surface of multiple myeloma cells, and the CD3 receptor found on the surface of cancer-fighting T cells, bridging them together to activate an immune response. Binding affinity to BCMA and CD3 has been optimized, enabling more potent T-cell-mediated anti-myeloma activity. Subcutaneous administration of PF-06863135 is intended to allow higher doses than intravenous administration without increasing adverse events.

The primary objectives of this portion of the study were to assess safety and tolerability of PF-06863135 administered subcutaneously, to determine the maximum tolerated dose, and to select the recommended Phase 2 dose. In the study, no dose-limiting toxicities were observed across any of the subcutaneous dose levels evaluated (80 to 1,000 μg/kg weekly) during dose escalation. Cytokine release syndrome (CRS) was reported in 73.3% of patients and was limited exclusively to grade 1 (56.7%) or grade 2 (16.7%). Grade 3 or higher adverse events (AEs) occurring in more than 10% of patients included lymphopenia (53.3%), neutropenia (26.7%), thrombocytopenia (16.7%) and anemia (16.7%).

The overall response rate (ORR) was 80% among the 20 patients treated in cohorts across the efficacious dose range of 215 to 1,000 μg/kg weekly. Among these 20 patients, six achieved stringent complete response or complete response, three achieved very good partial response, and six achieved partial response. Three responding patients had received at least one prior BCMA-targeted therapy. At the highest dose level of 1,000 μg/kg, the ORR was 83% (5/6 patients). Based on these data, 1,000 μg/kg weekly is the recommended Phase 2 dose.

About the PF-06863135 Phase 1 Trial

NCT03269136 is a Phase 1, open-label, multi-dose, multicenter, dose escalation, safety, pharmacokinetic (PK) and pharmacodynamic study of PF-06863135 for adult patients with advanced multiple myeloma who have relapsed after, or are refractory to, standard therapies. Part 1 of this two-part study assessed the safety and tolerability of increasing dose levels of PF-06863135. The study enrolled 80 patients and evaluates PF-06863135 administered intravenously or subcutaneously. Preliminary results for intravenous administration were reported at ASH (Free ASH Whitepaper) in 2019.1 For more information about the trial, visit www.clinicaltrials.gov.

About Multiple Myeloma

Multiple myeloma is a blood cancer that affects plasma cells made in the bone marrow. Healthy plasma cells make antibodies that help the body fight infection. According to the latest figures available, there are approximately 32,270 new cases of multiple myeloma diagnosed annually in the United States and 160,000 globally.2,3 Despite treatment advances, multiple myeloma remains incurable. The median survival is just over 5 years, and most patients receive four or more lines of therapy.4

On December 7, 2020 Schrödinger, Inc. (Nasdaq: SDGR), whose physics-based software platform is transforming the way therapeutics and materials are discovered, reported that preclinical data from its wholly-owned MALT1 inhibitor program in B-cell lymphomas at the virtual 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, Schrodinger, DEC 7, 2020, View Source [SID1234572362]). MALT1, mucosa-associated lymphoid tissue lymphoma translocation protein 1, is considered a potential therapeutic target for several non-Hodgkin’s B-cell lymphomas as well as chronic lymphocytic leukemia (CLL). Schrödinger scientists have identified novel MALT1 inhibitors that have shown strong anti-tumor activity in preclinical models alone and in combination with ibrutinib, a Bruton’s tyrosine kinase (BTK) inhibitor, and venetoclax, a B-cell lymphoma 2 (BCL-2) inhibitor, two anti-cancer therapies used to treat certain B-cell lymphomas and CLL.

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"We are pleased our MALT1 inhibitors indicate promising preclinical anti-cancer activity in diffuse large B-cell lymphomas, commonly called DLBCL, as a single agent or in combinations. Our data suggest our lead molecules may expand therapeutic options for lymphoma patients who need alternative therapeutic options after relapse or becoming resistant to existing agents," said Karen Akinsanya, Ph.D., Executive Vice President, Chief Biomedical Scientist and Head of Discovery R&D at Schrödinger. "Our preclinical work is ongoing, and we plan to advance this program into IND-enabling studies in the first half of 2021."

The discovery of lead molecules in Schrödinger’s MALT1 program was accelerated with the company’s differentiated, physics-based platform, which facilitates exploration of vast amounts of chemical space. Schrödinger’s free energy perturbation technology (FEP+) was used in combination with machine learning to prioritize billions of computer- and human-designed compounds to identify and optimize potent, selective inhibitors with favorable drug-like properties in under one year.

Additional Details About the Study

The presentation, "Identification of Potent Paracaspase MALT1 Inhibitors for Hematological Malignancies," highlighted preclinical data with multiple lead molecules discovered by Schrödinger scientists. The company’s MALT1 compounds showed potent in vitro inhibition of MALT1 enzymatic activity, with high binding affinity to the protein. Strong in vivo anti-tumor activity was observed in mouse xenograft models of DLBCL. Additionally, strong in vivo anti-proliferative effects were reported in combination with ibrutinib and venetoclax in mouse models. Taken together, these data provide further rationale for developing MALT1 inhibitors as a potential therapeutic approach particularly in combination with existing therapies to potentially treat relapsed/refractory B-cell lymphoma and difficult to treat blood cancers such as DLBCL.