On September 29, 2020 Dewpoint Therapeutics, the biomolecular condensates company, reported it has raised $77 million in a Series B financing (Press release, Dewpoint Therapeutics, SEP 29, 2020, View Source [SID1234567776]). The round was led by ARCH Venture Partners, with participation from new investors Maverick Ventures and Bellco Capital, and existing investors Leaps by Bayer, EcoR1 Capital, Polaris Partners, Samsara BioCapital, and Innovation Endeavors.

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"We are delighted to have ARCH Venture Partners lead this financing, and to welcome new investors into the condensate field," said Amir Nashat, managing partner of Polaris Partners and interim CEO of Dewpoint. "Our proprietary platform has already generated two significant external collaborations with Merck and Bayer, and today’s announcement underscores the interest in biomolecular condensates among investors with a track record of backing groundbreaking science."

Dewpoint’s proprietary condensates platform provides the ability to see and understand the complex interactions of biomolecular communities—and to find drugs that intervene in entirely new ways. Dewpoint will use proceeds from this round to further develop its platform and identify additional compounds that modulate these condensates.

"Dewpoint is the international center of gravity for developing and translating condensate science into drugs," said Kristina Burow, managing director at ARCH Venture Partners. "The company is well positioned to leverage novel insights into fundamental biology and utilize this groundbreaking biology to create transformational therapeutics."

"The Dewpoint team is a unique combination of executives who have brought more than ten drugs to market and researchers who have spent the last several years defining the science of condensates," said Oleg Nodelman, founder and portfolio manager of EcoR1 Capital. "This collection of drug hunters is a powerful force."

In addition to announcing its Series B, Dewpoint reported the addition of Giuseppe Ciaramella, Ph.D., to its Board of Directors. Ciaramella is president and chief scientific officer of Beam Therapeutics. Prior to Beam, Dr. Ciaramella served at Moderna, first as head of immunology and biotherapeutics, then as chief scientific officer of its infectious diseases division. Prior to Moderna, he held senior drug development roles at AstraZeneca, Boehringer Ingelheim, and Pfizer. Dr. Ciaramella holds a B.Sc. and Ph.D. in biochemistry and molecular biology from University College London.

Dewpoint’s proprietary platform uses high-throughput methods to test libraries of potential drugs for the desired effect, identifying compounds that modulate biomolecular condensates in specific diseases of immediate interest to Dewpoint and its partners. Approaches to modulating condensates that may positively impact disease include dissolving or forming condensates, modulating the composition of condensates, stabilizing condensates, and selective drug delivery into condensates.

In July 2020, Dewpoint announced an exclusive collaboration with Merck (MSD) to leverage Dewpoint’s proprietary biomolecular condensate platform for the development of a novel mechanism for the treatment of HIV. In November 2019, Dewpoint announced a collaboration with Bayer, combining the potential of Dewpoint’s condensate platform with Bayer’s small molecule compound library to develop new treatments for cardiovascular and gynecological diseases.

In addition to disease areas where Dewpoint has announced collaborations, the company is exploring potential therapeutic opportunities in oncology, neurodegeneration, metabolic disease, and immunology.

On September 29, 2020 Medtronic plc (the "Company") (NYSE:MDT) reported that its wholly-owned subsidiary Medtronic Global Holdings S.C.A. ("Medtronic Luxco") has closed a registered public offering (the "Offering") of €1,250,000,000 principal amount of 0.000% Senior Notes due 2023, €1,000,000,000 principal amount of 0.000% Senior Notes due 2025, €1,000,000,000 principal amount of 0.375% Senior Notes due 2028, €1,000,000,000 principal amount of 0.750% Senior Notes due 2032, €1,000,000,000 principal amount of 1.375% Senior Notes due 2040 and €1,000,000,000 principal amount of 1.625% Senior Notes due 2050 (collectively, the "Notes") (Press release, Medtronic, SEP 29, 2020, View Source [SID1234567775]). All of Medtronic Luxco’s obligations under the Notes are fully and unconditionally guaranteed by the Company and Medtronic, Inc. ("Medtronic, Inc."), a wholly-owned indirect subsidiary of Medtronic Luxco, on a senior unsecured basis.

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The net proceeds from the Offering are approximately €6.2 billion, after deducting underwriting discounts and commissions and estimated expenses related to the Offering payable by Medtronic Luxco. The net proceeds of the Offering will be used to repay €750 million aggregate principal amount of Medtronic Luxco’s Floating Rate Senior Notes due 2021 at maturity on March 7, 2021, which bore interest at a rate of 0% per annum at July 31, 2020, and to redeem the outstanding senior notes issued by Medtronic Luxco, Medtronic, Inc. and Covidien International Finance S.A., a wholly-owned indirect subsidiary of the Company as described below. Any remaining net proceeds of the Offering will be used for repayment of other indebtedness and general corporate purposes.

Today, the Company also announced that it intends to redeem all of the outstanding $1.5 billion aggregate principal amount of Medtronic, Inc.’s 3.150% Senior Notes due 2022, all of the outstanding $530.2 million aggregate principal amount of Medtronic, Inc.’s 2.750% Senior Notes due 2023, all of the outstanding $432.5 million aggregate principal amount of Medtronic, Inc.’s 3.625% Senior Notes due 2024, $810 million of the outstanding $2.7 billion aggregate principal amount of Medtronic, Inc.’s 3.500% Senior Notes due 2025, all of the outstanding $650 million aggregate principal amount of CIFSA’s 3.200% Senior Notes due 2022, all of the outstanding $309.5 million aggregate principal amount of CIFSA’s 2.950% Senior Notes due 2023 and all of the outstanding €1.5 billion aggregate principal amount of Medtronic Luxco’s 0.000% Senior Notes due 2021 (collectively, the "Redemption Notes"), in each case at the make-whole redemption prices specified in, and otherwise in accordance with, the indentures governing such Redemption Notes. The redemption date for the Redemption Notes will be October 29, 2020. This press release does not constitute a notice of redemption of any of the Redemption Notes.

On September 29, 2020 LC-SCRUM-Asia, a leading cancer genomic screening program, reported that it has selected Thermo Fisher Scientific’s Ion Torrent Genexus System* and Oncomine Precision Assay*, a pan-cancer panel, to advance precision medicine in Asia (Press release, Thermo Fisher Scientific, SEP 29, 2020, View Source [SID1234567774]). The next-generation sequencing (NGS) solutions will be used in two prospective, observational projects to support the development of future therapeutics and diagnostics for non-small cell lung cancer (NSCLC).

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The Lung Cancer Genomic Screening Project for Individualized Medicine in Asia aims to overcome challenges in establishing precision medicine for patients with NSCLC through large-scale genetic screening and monitoring. The Lung Cancer Genomic Screening Project for Individualized Medicine – Molecular Testing for Resistant Tumors to Systemic Therapy (LC-SCRUM-TRY), newly launched on September 28, is designed to examine drug resistance in NSCLC.

"The studies will use the Genexus System and the Oncomine Precision Assay for rapid molecular profiling results," said Dr. Koichi Goto, chief of the Department of Thoracic Oncology, National Cancer Center Hospital East, who is leading the cancer clinical trials. "The speed of NGS-based molecular profiling tests is becoming increasingly important. We believe these solutions, designed to deliver results quickly, will transform the field of precision oncology."

Thermo Fisher’s Ion Torrent Genexus System is the first fully integrated NGS platform featuring an automated specimen-to-report workflow that delivers results economically in a single day. The Oncomine Precision Assay, which is designed to detect key biomarkers from formalin-fixed paraffin-embedded (FFPE) tissue and liquid biopsy specimens, contains more than 50 cancer-related biomarkers and has the lowest sample input requirements on the market for detection of both DNA and RNA variants.

Garret Hampton, president of clinical next-generation sequencing and oncology at Thermo Fisher Scientific, said, "Through our valued partnership with LC-SCRUM, Dr. Goto and his team have a pivotal opportunity to advance precision medicine for non-small cell lung cancer in Asia. Expanding access to comprehensive genomic profiling will help improve the future standard of care."

The selection of the Genexus System and Oncomine Precision Assay represent an extension of Thermo Fisher’s ongoing collaborations with LC-SCRUM and Dr. Goto to make precision medicine solutions available in Japan. Since 2015, LC-SCRUM has adopted the Oncomine Comprehensive Assay* for use in the first three phases of clinical trials. In addition, Dr. Goto was instrumental in supporting Thermo Fisher’s efforts to gain approval in Japan for the Oncomine Dx Target Test, the first NGS companion diagnostic (CDx) test approved by the Ministry of Health, Labor and Welfare (MHLW) to simultaneously detect multiple biomarkers clinically associated with NSCLC.

On September 29, 2020 BioMarin Pharmaceutical Inc. (NASDAQ: BMRN) reported that Brian Mueller, Executive Vice President, Chief Financial Officer, will participate in Morningstar’s Management Behind the Moat Conference on September 30, 2020 at 1:00pm ET (Press release, BioMarin, SEP 29, 2020, View Source [SID1234567773]). An audio webcast of the presentation will be available live. You can access the webcast at: View Source An archived version of the remarks will also be available through the Company’s website for a limited time following the conference.

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On September 29, 2020 Hackensack Meridian Health reported that A one-two punch of changing gene expression, then deploying immune checkpoint inhibitors, shows promise in battling one of the most treatment-resistant types of cancer in preclinical models (Press release, Hackensack Meridian Health, SEP 29, 2020, View Source [SID1234567772]).

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Their research findings published Aug. 14 in the journal Cancer Research suggest that since some cancer treatments can be undermined by epigenetic changes (altered DNA methylation affecting gene expression) in cancer cells before the treatments are even administered, a worthwhile strategy is to administer an epigenetically-acting drug – which can pave the way for more effective subsequent use of immune-acting cancer treatments, the authors found.

"Overall, these findings in a model of aggressive pancreatic cancer have clear and promising implications for the design of future studies, both in mice and in human patients, to improve the effectiveness of epigenetic modulation, in combination with immune checkpoint inhibition," said Benjamin Tycko, M.D., Ph.D., the CDI lab director who oversaw the study, along with his longtime colleague Tamas Gonda, M.D. "They also suggest a clear path forward for making further improvements."

The tumor type – pancreatic ductal adenocarcinoma – is among the most deadly cancer types, since it has proven to be stubbornly resistant both to standard chemotherapy and more recent immunotherapies.

The researchers tested four protocols, which included the sequential use of decitabine, a DNA-hypomethylating drug, followed by immune checkpoint inhibitors. Among the effects documented in the data: the increase in crucial, and tumor-infiltrating, effector T cells, with this one-two punch.

Compared against the control group, there were no adverse side effects of adding decitabine, and the one-two punch of decitabine and the immune-acting agents doubled the average survival time in the model.

However, treatment was still not a cure, and the cancers ultimately progressed – perhaps partly because of a decitabine-induced increase in M2 macrophages, immune system cells which can inhibit therapeutic responses.

The researchers’ work continues, with further strategies including adding other epigenetic drugs, and also discovering ways to reduce the number of M2 macrophages – to potentially improve the response.

Authors of the study include colleagues from Columbia University, who have started working on an early-phase clinical trial in relation to the therapeutic combination. Additionally, motivated by the findings in pancreatic cancer, scientists at the CDI are now at work applying a similar approach in a multiple myeloma model. They are also starting new collaborations with investigators working on pancreatic cancer at the Georgetown Lombardi Comprehensive Cancer Center. John Theurer Cancer Center of Hackensack Meridian Health is a member of the Georgetown Lombardi Comprehensive Cancer Center Consortium.

A DNA hypomethylating drug alters the tumor microenvironment and improves the effectiveness of immune checkpoint inhibitors in a mouse model of pancreatic cancer.
Gonda TA, Fang J, Salas M, Do C, Hsu E, Zhukovskaya A, Siegel A, Takahashi R, Lopez-Bujanda ZA, Drake CG, Manji GA, Wang TC, Olive KP, Tycko B.Cancer Res. 2020 Aug 14:canres.0285.2020. doi: 10.1158/0008-5472.CAN-20-0285.