On November 18, 2021 Dicerna Pharmaceuticals, Inc. (Nasdaq: DRNA) reported that it has entered into a definitive agreement with Novo Nordisk under which Novo Nordisk will acquire Dicerna, a biopharmaceutical company focused on the development of investigational ribonucleic acid interference (RNAi) therapeutics, for $38.25 per share in cash, which represents a total equity value of $3.3 billion and a premium of 80% to Dicerna’s closing price on November 17, 2021 (Press release, Dicerna, NOV 18, 2021, View Source [SID1234595777]). The transaction was unanimously approved by the Dicerna Board of Directors and the Board of Directors of Novo Nordisk.

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Novo Nordisk and Dicerna have been parties to a research collaboration since 2019 to discover and develop RNAi therapies using Dicerna’s proprietary GalXC RNAi platform technology. The collaboration between Novo Nordisk and Dicerna encompassed the exploration of more than 30 liver cell targets with the potential to deliver multiple clinical candidates for disorders including chronic liver disease, non-alcoholic steatohepatitis (NASH), type 2 diabetes, obesity and rare diseases. Novo Nordisk expects to initiate clinical development of the first investigational RNAi therapeutic to emerge from this collaboration in 2022.

Dicerna’s RNAi technology platform enables access to intracellular disease targets across hepatic and extrahepatic cell and tissue types, complementing Novo Nordisk’s existing technology platforms. This acquisition supports Novo Nordisk’s strategy of developing and applying a broad range of technology platforms across all Novo Nordisk therapeutic areas.

"The acquisition of Dicerna accelerates Novo Nordisk’s research within RNAi and expands the usage of the RNAi technology," said Marcus Schindler, Executive Vice President and Chief Scientific Officer of Novo Nordisk. "We build on our successful collaboration and by combining Dicerna’s state-of-the-art RNAi drug engine and intracellular delivery with our deep capabilities in disease biology understanding and tissue targeting through peptides and proteins we have the potential to expand our pipeline and deliver life-changing precision medicines for people living with chronic diseases such as diabetes, obesity, cardiovascular disease and NASH, as well as rare diseases like endocrine disorders and bleeding disorders."

"Since the start of our collaboration two years ago, the Dicerna and Novo Nordisk teams have established a strong rapport built on a foundation of mutual respect for one another’s capabilities, culture and expertise," said Douglas Fambrough, Ph.D., Founder, President and Chief Executive Officer of Dicerna. "The combination of Dicerna’s expertise in RNAi and oligonucleotide therapeutics and highly skilled employees with Novo Nordisk’s industry leadership in developing and commercializing medicines to treat serious chronic diseases, has the potential to significantly accelerate and expand our mission to deliver GalXC RNAi therapies for the benefit of patients and all our stakeholders."

Under the terms of the agreement, Novo Nordisk, through a subsidiary, will initiate a tender offer to acquire all outstanding shares of Dicerna common stock at a price of $38.25 per share in cash. The closing of the tender offer will be subject to certain conditions, including the tender of shares representing at least a majority of the total number of Dicerna’s outstanding shares, the expiration of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act and other customary conditions. Upon the successful completion of the tender offer, Novo Nordisk’s acquisition subsidiary will be merged into Dicerna, and any remaining shares of common stock of Dicerna will be cancelled and converted into the right to receive the same $38.25 per share price payable in the tender offer. The transaction is expected to close in the fourth quarter of 2021.

Novo Nordisk is represented by Evercore as exclusive financial advisor and Davis Polk & Wardwell LLP as legal advisor. For Dicerna, Centerview Partners LLC is acting as lead financial advisor, SVB Leerink is acting as financial advisor, and Skadden, Arps, Slate, Meagher & Flom LLP and Goodwin Procter LLP are acting as legal advisors.

On November 18, 2021 Plus Therapeutics, Inc. (Nasdaq: PSTV) (the "Company"), a U.S. clinical-stage pharmaceutical company developing innovative, targeted radiotherapeutics for rare and difficult-to-treat cancers, reported that positive interim data on its lead investigational drug, Rhenium-186 NanoLiposome (186RNL), from the first-in-man Phase 1 ReSPECT-GBM clinical trial in patients with recurrent glioblastoma (GBM) at the 2021 Society for Neuro-Oncology Annual Meeting and Education Day being held in Boston, Massachusetts (Press release, Cytori Therapeutics, NOV 18, 2021, View Source [SID1234595776]).

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According to the interim data, 186RNL delivered via convection enhanced delivery (CED) is well-tolerated with favorable overall survival in adult patients at higher absorbed radiation doses (greater than 100 Gy). A positive correlation was observed between overall survival and higher absorbed radiation doses (greater than 100 Gy).

The poster, titled "Safety and Feasibility of Rhenium-186 NanoLiposome (186RNL) in Recurrent Glioma: the ReSPECT Phase 1 Trial," outlines data from the ReSPECTTM-GBM trial, substantially funded by the U.S. National Institutes of Health/National Cancer Institute, which has thus far evaluated 22 adult patients with recurrent GBM across seven cohorts of increasing dose, treated over a six year period.

"In the ReSPECTTM trial thus far, 186RNL has been well-tolerated without dose-limiting toxicities and we believe further clinical investigation of relative efficacy is warranted," said Andrew J. Brenner, M.D., Ph.D., Professor of Medicine, Neurology, and Neurosurgery at The University of Texas Health Science Center at San Antonio and principal investigator of the ReSPECT-GBM clinical trial. "The open label, dose escalation trial was not designed to show efficacy but the trends observed between overall survival and key delivery parameters such as therapeutic radiation dose to the tumor are promising."

Key findings include the following:

No delivery failures were observed and an average absorbed dose of 267.5 Gy (range 8.9-740Gy) of radiation was delivered to the tumor.
No dose limiting toxicities or adverse events (AEs) with the outcome of death, or discontinuations due to AEs have been observed.
Of 22 total subjects with recurrent GBM treated with 186RNL, seven patients remain alive and mean and median overall survival (OS) is currently 336.6 days and 231.5 days, respectively.
In the subset of 13 patients receiving greater than 100 Gy absorbed radiation, seven patients remain alive and mean and median OS is currently at 453.8 days and 330 days respectively.
No patients remain alive in the cohort of 9 patients receiving less than 100 Gy absorbed radiation and mean and median OS is 167.3 days and 156 days respectively.
In 10 treated patients in cohorts five through seven, 13.4 millicuries or more of radiation was delivered and 80% received greater than 100 Gy average absorbed dose of radiation to the tumor.
"Our team is pleased with the clinical performance and the potential promise of 186RNL in patients with this devastating disease," said Marc Hedrick, M.D., President and Chief Executive Officer of Plus Therapeutics. "In particular, the observation that we may be able to reliably and precisely deliver a significant therapeutic dose of radiation greater than 100 Gy and potentially influence survival is a positive development. We look forward to completing key drug scale-up activities and proceed to FDA discussions regarding CMC and next clinical steps in early 2022."

For a more detailed discussion of the ReSPECT-GBM trial data, please join the Plus Therapeutics hosted webinar on Thursday, November 18, 2021, 4:00 to 5:00 p.m. ET (details below).

A copy of the poster will be available under the Presentations tab of the Investors section of the Company’s website at View Source

Key Opinion Leader Roundtable Webinar Details

A live webinar with accompanying slides will be available in the Events page of the Investor Relations section of the Plus Therapeutics website. Individuals can participate in an interactive Q&A session by submitting pertinent questions via the webcast platform.

Please log in approximately 10 minutes prior to the scheduled start time of 4:00 p.m. ET on November 18, 2021. The archived webcast will be available in the Events section of the Company’s website for 90 days.

A live audio conference will be available by dialing (833) 340-0285 (toll-free) or (236) 712-2475 and entering Conference ID 3170796.

About Rhenium-186 NanoLiposome

Rhenium-186 NanoLiposome (186RNL) is under investigation as a potentially safe, effective and convenient way to deliver a very high dose of radiation, possibly over 20 times greater than traditional external beam radiation therapy. This trial is supported by the U.S. National Institutes of Health/National Cancer Institute at three trial sites in the U.S., including UT Health Science Center San Antonio, UT Southwestern Medical Center Dallas and UT MD Anderson Cancer Center Houston.

The U.S. Food and Drug Administration has granted both Orphan Drug designation and Fast Track designation to 186RNL for the treatment of patients with GBM. Additional details about the ReSPECT trial are available at clinicaltrials.gov (NCT01906385).

On November 18, 2021 Tempest Therapeutics, Inc. (Nasdaq: TPST), a clinical-stage oncology company developing potentially first-in-class therapeutics that combine both tumor-targeted and immune-mediated mechanisms, reported the first patient has been dosed with TPST-1495 in combination with pembrolizumab in the Phase 1a/1b open-label, dose and schedule optimization study of TPST-1495 in patients with solid tumors (Press release, Tempest Therapeutics, NOV 18, 2021, View Source [SID1234595775]).

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"We’re very pleased to announce the start of patient dosing with TPST-1495 in combination with pembrolizumab," said Sam Whiting, MD, Ph.D., chief medical officer of Tempest. "TPST-1495 is designed to inhibit key components of the Prostaglandin E2, or PGE2, pathway, which is both a driver of tumor cell proliferation and an important suppressor of anti-tumor immune function. In addition, recent data show that PGE2 is involved in enabling tumors to escape from immune checkpoint inhibitors such as pembrolizumab, a process known as adaptive immune resistance. Based on this mechanistic rationale and our preclinical data, we are excited about the potential of this combination to be superior to either approach alone and bring benefit to patients."

The first-in-human Phase 1a/1b, multicenter, open-label, dose and schedule optimization study is being conducted at academic and Phase 1 sites in the U.S. and evaluates TPST-1495 as a single agent and in combination with pembrolizumab to determine its maximum tolerated dose and/or recommended Phase 2 dose, safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary anti-tumor activity in subjects with advanced solid tumors. The preliminary dose-finding stage of the study allows patients with any solid tumor histology, while the study expansion stages are designed both to focus upon patients with prostaglandin-driven cancers, including colorectal cancer, endometrial cancer, squamous cell carcinoma of the head and neck, as well as biomarker-selected patients with tumor-driver mutations in the PIK3CA gene, which are known to enhance the level of prostaglandin production in tumor cells.

About TPST-1495

TPST-1495 is an orally available small molecule designed to block the tumor-promoting EP2 and EP4 receptors in the prostaglandin (PGE2) pathway, while sparing the homologous but immune-supporting EP1 and EP3 receptors. PGE2 signaling through EP2 and EP4 has been observed both to enhance tumor progression and promote immune suppression. Tempest has conducted head-to-head preclinical studies comparing TPST-1495 to single antagonists of EP2 and EP4 and observed significantly enhanced activity of TPST-1495 in both overcoming PGE2-mediated suppression of human immune cells in vitro, as well as significantly increased anti-tumor activity in mouse models of human colorectal cancer. Tempest is currently evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and possible anti-tumor activity of TPST-1495 as a single agent and in combination with pembrolizumab in a multicenter Phase 1a/1b dose and schedule optimization study in subjects with advanced solid tumors.

On November 18, 2021 BridgeBio Pharma, Inc. (Nasdaq: BBIO) (BridgeBio or the Company), a commercial-stage biopharmaceutical company focused on genetic diseases and cancers, reported that it has executed a definitive credit facility agreement with a syndicate of lenders for up to $750.0 million in financing (Press release, BridgeBio, NOV 18, 2021, View Source [SID1234595774]).

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This facility, combined with the Company’s existing cash balance as of September 30, 2021, provides access to over $1.2 billion to advance the Company’s pipeline programs, support commercialization efforts, and enable the Company to pursue strategic business development opportunities. As structured, this financing is expected to fully fund BridgeBio’s portfolio of more than 30 drug development and discovery programs into 2024, independent of near-term milestone readouts. It is a significant achievement in BridgeBio’s broader efforts to attract diverse sources of capital to fund life science innovation and is aligned with its long-term strategy of creating non-dilutive financing pathways that leverage portfolio readouts—in addition to cash balance on hand—to extend runway.

This financing announcement follows BridgeBio’s repurchase of approximately $150.0 million in its own common stock under its 2021 Share Repurchase Program, completing about $385.6 million of equity and capped call purchases in the aggregate since its initial public offering in 2019. In addition, today’s financing replaces the Company’s $100.0 million debt facility with Hercules. Collectively, these transactions represent a strategic recapitalization of the Company ahead of upcoming clinical data readouts.

"We are grateful to have the support of debt investors who are committed to helping us build the next great genetic medicine company and deliver meaningful therapies for patients in need. Since our founding, we have believed in the power and importance of innovative financing approaches to advance critical biomedical research and drug development, and we are grateful that our broad diversified pipeline enables us to do this. By bringing on this additional capital, we have the potential to help more people living with genetic diseases and cancers as quickly as possible," said Brian Stephenson, Ph.D., CFA, BridgeBio’s Chief Financial Officer.

"Potential breakthrough medicines should never languish on the shelf because of a lack of funding. By seizing inventive financing tools to fund its growing R&D pipeline, BridgeBio is working to ensure that promising medicines in development can advance into the clinic and toward potential commercial approval. The Company’s groundbreaking approach to science and finance has made it a leader within the biotech industry and we are hopeful there are new methods we can explore to more fully unlock the power of investors to help patients," said Andrew Lo, Ph.D., a BridgeBio co-founder and a member of the Company’s board of directors.

Key features of the credit facility include:

$450.0 million funded on November 17, 2021

An additional $300.0 million to be funded at the Company’s option following either 1) positive topline results from Part A of its Phase 3 ATTRibute-CM trial of TTR stabilizer for transthyretin amyloid cardiomyopathy (ATTR-CM), which is expected by the end of the year, OR 2) positive proof-of-concept data for various pipeline programs by year end 2022, with $100.0 million available upon each proof-of-concept, for up to three pipeline programs

Fixed interest rate of 9%, with 3% eligible at the Company’s discretion to be paid in kind and added to principal

Maturity date of November 17, 2026

Interest-only period for three years, which may be extended to four years upon success of the Part A readout

Substantial flexibility for future business development, M&A, share repurchases, and royalty transactions

No financial covenants

Morgan Stanley & Co. LLC acted as the sole placement agent to BridgeBio on this transaction.

Latham & Watkins LLP acted as counsel to BridgeBio.

On November 18, 2021 Crinetics Pharmaceuticals, Inc. (Nasdaq: CRNX), a clinical stage pharmaceutical company focused on the discovery, development and commercialization of novel therapeutics for rare endocrine diseases and endocrine-related tumors, reported that company management will participate in a fireside chat and one-on-one investor meetings at the 4th Annual Evercore ISI HealthCONx Conference, which is taking place virtually November 30, 2021 through December 2, 2021 (Press release, Crinetics Pharmaceuticals, NOV 18, 2021, https://crinetics.com/crinetics-presents-at-evercore-isi-healthconx-111821/ [SID1234595773]).

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Details on the fireside chat can be found below.

Date: December 2, 2021
Time: 12:35 PM ET
Webcast Link: View Source
A webcast of the fireside chat will also be accessible on the Events & Presentations page in the Investors section of the Crinetics website. A replay of the fireside chat will be available at the same location following its conclusion and will be archived for 90 days.