On March 16, 2021 Merck (NYSE: MRK), known as MSD outside the United States and Canada, reported that the U.S. Food and Drug Administration (FDA) has accepted and granted priority review for a New Drug Application (NDA) for the hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor belzutifan (pronounced bell-ZOO-ti-fan), a novel investigational candidate in Merck’s oncology pipeline, for the potential treatment of patients with von Hippel-Lindau (VHL) disease-associated renal cell carcinoma (RCC), not requiring immediate surgery (Press release, Merck & Co, MAR 16, 2021, View Source [SID1234576713]). This NDA is based on data from the Phase 2 Study-004 trial, in which belzutifan showed a confirmed overall response rate of 36.1% (n=22/61) (95% CI: 24.2-49.4) in patients with VHL disease-associated RCC. The FDA has set a Prescription Drug User Fee Act (PDUFA), or target action, date of September 15, 2021.

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"Von Hippel-Lindau disease is a rare genetic condition for which there is no systemic treatment option available and is associated with a high risk of cancer development in multiple organs. In fact, up to 70% of patients with VHL develop renal cell carcinoma during their lifetime," said Dr. Scot Ebbinghaus, vice president, clinical research, Merck Research Laboratories. "This priority review validates the important progress we have made to expand and diversify Merck’s oncology pipeline with innovative, new therapeutic approaches. We look forward to working closely with the FDA to bring belzutifan to patients in need."

Merck is also studying belzutifan in advanced RCC and other tumor types through a broad clinical program. In addition to the ongoing Phase 2 Study-004 trial, belzutifan is being evaluated in Phase 3 trials as monotherapy and as part of a combination regimen in previously treated patients and as part of a combination regimen as a first-line treatment for advanced clear cell RCC.

About the Phase 2 Study-004 Trial

This application is based on data from Study-004 (ClinicalTrials.gov, NCT03401788), which is a Phase 2, open-label trial evaluating belzutifan for the potential treatment of patients with VHL disease who had at least one measurable solid tumor localized to the kidney and who did not require immediate surgery. The study enrolled 61 patients who received belzutifan 120 mg orally once daily until disease progression or unacceptable toxicity. The primary endpoint was objective response rate in VHL disease-associated RCC. Secondary endpoints in RCC tumors include disease control rate, duration of response, time to response, progression-free survival, time to surgery and safety.

Additionally, this study evaluated response rates in other common VHL disease-associated tumors, including pancreatic cysts, pancreatic neuroendocrine tumors, central nervous system (CNS) hemangioblastomas, and retinal hemangioblastomas.

About Belzutifan

Belzutifan (MK-6482) is a novel, potent and selective inhibitor of HIF-2α. Proteins known as hypoxia-inducible factors, including HIF-2α, can accumulate in patients when VHL, a tumor-suppressor protein, is inactivated. If not properly regulated, the accumulation of HIF-2α can stimulate several oncogenes associated with cellular proliferation, angiogenesis and tumor growth, leading to the growth of both benign and malignant tumors. This inactivation of VHL has been observed in more than 90% of clear cell RCC tumors. Research into VHL biology that led to the discovery of HIF-2α was awarded the Nobel Prize in Physiology or Medicine in 2019.

About Von Hippel-Lindau Disease and Renal Cell Carcinoma

Von Hippel-Lindau disease is a rare genetic disease that affects one in 36,000 people (200,000 cases worldwide and 10,000 cases in the U.S. alone). Patients with VHL disease are at risk for benign blood vessel tumors as well as several cancers, including RCC. As many as 70% of people with VHL disease develop RCC.

Renal cell carcinoma is by far the most common type of kidney cancer; about nine of 10 kidney cancers are RCCs, and about seven of 10 RCCs are clear cell. Worldwide, it is estimated there were nearly 431,300 cases of kidney cancer diagnosed and almost 179,400 deaths from the disease in 2020. In the U.S. alone, it is estimated there will be almost 76,100 new cases of kidney cancer diagnosed and nearly 13,800 deaths from the disease in 2021.

Merck’s Focus on Cancer

Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, the potential to bring new hope to people with cancer drives our purpose and supporting accessibility to our cancer medicines is our commitment. As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the largest development programs in the industry across more than 30 tumor types. We also continue to strengthen our portfolio through strategic acquisitions and are prioritizing the development of several promising oncology candidates with the potential to improve the treatment of advanced cancers. For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.

On March 16, 2021 MannKind Corporation (Nasdaq: MNKD) reported that on March 15, 2021 it issued an additional $30.0 million aggregate principal amount of 2.50% Convertible Senior Notes due 2026 (the "notes") pursuant to the exercise in full of the initial purchasers’ option in connection with MannKind’s previously-announced private placement (the "offering") to qualified institutional buyers pursuant to Rule 144A under the Securities Act of 1933, as amended (the "Securities Act") (Press release, Mannkind, MAR 16, 2021, View Source [SID1234576712]). After giving effect to the additional sale of notes pursuant to the exercise in full of the initial purchasers’ option, MannKind estimates that the total net proceeds from the offering were approximately $222.9 million, after deducting the initial purchasers’ discounts and commissions and estimated offering expenses.

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The notes are general unsecured obligations of MannKind and will accrue interest at a rate of 2.50% per annum, payable semiannually in arrears on March 1 and September 1 of each year, beginning on September 1, 2021. The notes will mature on March 1, 2026, unless earlier converted, redeemed or repurchased.

Before December 1, 2025, holders will have the right to convert their notes only upon the occurrence of certain events. From and after December 1, 2025, until the close of business on the business day immediately preceding the maturity date, holders will have the right to convert all or any portion of their notes at their election. Upon conversion, MannKind will pay or deliver, as the case may be, cash, shares of MannKind’s common stock or a combination of cash and shares of MannKind’s common stock, at its election. The initial conversion rate is 191.8281 shares of common stock per $1,000 principal amount of notes, which represents an initial conversion price of approximately $5.21 per share of common stock. The initial conversion price represents a premium of approximately 30% over the last reported sale of $4.01 per share of MannKind’s common stock on March 1, 2021. The conversion rate and conversion price will be subject to adjustment upon the occurrence of certain events.

MannKind may not redeem the notes prior to March 6, 2024. MannKind may redeem for cash all or any portion of the notes (subject to certain limitations), at its option, on or after March 6, 2024 and prior to the 36th scheduled trading day immediately preceding the maturity date, if the last reported sale price of MannKind’s common stock has been at least 130% of the conversion price then in effect for at least 20 trading days (whether or not consecutive) during any 30 consecutive trading day period (including the last trading day of such period) ending on, and including, the trading day immediately preceding the date on which MannKind provides notice of redemption at a redemption price equal to 100% of the principal amount of the notes to be redeemed, plus accrued and unpaid interest to, but excluding, the redemption date.

If a "fundamental change" (as defined in the indenture for the notes) occurs, then, subject to limited exceptions, holders may require MannKind to repurchase their notes for cash. The repurchase price would be equal to the principal amount of the notes to be repurchased, plus accrued and unpaid interest, if any, to, but excluding, the applicable repurchase date.

MannKind intends to use the net proceeds from the offering for working capital and other general corporate purposes, including a Phase 3 clinical trial of Afrezza in pediatric subjects and further development of product candidates in MannKind’s pipeline. MannKind may also use a portion of the proceeds from the offering to pay down a portion of existing debt or for acquisitions or strategic investments in complementary businesses or technologies, although MannKind does not currently have any plans for any such debt repayment, acquisitions or investments.

The notes and any shares of MannKind’s common stock issuable upon conversion of the notes have not been and will not be registered under the Securities Act, any state securities laws or the securities laws of any other jurisdiction, and unless so registered, may not be offered or sold in the United States absent registration or an applicable exemption from, or in a transaction not subject to, the registration requirements of the Securities Act and other applicable securities laws.

This press release is neither an offer to sell nor a solicitation of an offer to buy any of these securities nor shall there be any sale of these securities in any state or jurisdiction in which such an offer, solicitation or sale would be unlawful prior to the registration or qualification thereof under the securities laws of any such state or jurisdiction.

On March 16, 2021 Innate Pharma SA (Euronext Paris: IPH – ISIN: FR0010331421; Nasdaq: IPHA) ("Innate" or the "Company"), reported that the Company will hold a conference call on Thursday, March 18, 2021 at 2 p.m. CET / 9 a.m. ET, following the release of its financial results for the full year ending December 31, 2020 (Press release, Innate Pharma, MAR 16, 2021, View Source [SID1234576710]).

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Presenting during the call will be Innate Pharma’s Chief Executive Officer Mondher Mahjoubi, MD, Chief Financial Officer Laure-Hélène Mercier and Chief Medical Officer Joyson Karakunnel, MD, MSc, FACP.

Details for the Virtual Event

The live webcast will be available at the following link:
View Source

Participants may also join via telephone to ask questions by registering in advance of the event at View Source Upon registration, participants will be provided with dial-in numbers, a direct event passcode and a unique registrant ID that they may use 10 minutes prior to the event start to access the call. Call reminders will also be sent to registered participants via e-mail the day prior to the event.

This information can also be found on the Investors section of the Innate Pharma website, www.innate-pharma.com. A replay of the webcast will be available on the Company website for 90 days following the event.

On March 16, 2021 Merck, a leading science and technology company, reported that topline data from the Phase II INTR@PID BTC 047 study evaluating bintrafusp alfa as a monotherapy in the second-line treatment of patients with locally advanced or metastatic biliary tract cancer (BTC) who have failed or are intolerant of first-line platinum-based chemotherapy (Press release, Merck & Co, MAR 16, 2021, View Source [SID1234576709]).

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In the study of 159 patients, bintrafusp alfa demonstrated single-agent efficacy and durability with a manageable safety profile after more than nine months of follow-up, with an Independent Review Committee (IRC)-adjudicated objective response rate (ORR) of 10.1% (95% CI: 5.9% to 15.8%) per RECIST 1.1. Though single-agent activity was observed, the study did not meet the pre-defined threshold that would have enabled regulatory filing for BTC in the second line setting. The results will be submitted for presentation at an upcoming medical meeting or publication.

"Given the high unmet treatment need in BTC, where single agent immunotherapy in PD-L1 all comers has shown an ORR of 5.8%, we are encouraged by the single agent clinical activity of bintrafusp alfa in this study as a second-line treatment," said Milind Javle, MD, professor of GI medical oncology, MD Anderson Cancer Center, and an investigator for the INTR@PID BTC 047 study. "The bintrafusp alfa 047 study is one of the most important clinical investigations conducted for chemo-refractory biliary cancers, and I would like to thank the patients, families, and study team for their valuable participation."

"This study demonstrates single-agent activity with bintrafusp alfa in locally advanced or metastatic BTC, a disease that has been historically difficult to treat," said Danny Bar-Zohar, M.D., Global Head of Development for the Healthcare business sector of Merck. "The data will contribute to our understanding of addressing both TGF-β and PD-L1 inhibition in the tumor microenvironment."

A Phase II/III study of bintrafusp alfa in combination with chemotherapy as a first-line treatment for BTC (INTR@PID BTC 055), which is assessing a different hypothesis than the second-line monotherapy study, has completed enrollment in the Phase II portion and is currently ongoing.

*Bintrafusp alfa is currently under clinical investigation and not approved for any use anywhere in the world.

About Biliary Tract Cancer (BTC)

BTCs are a group of rare, aggressive gastrointestinal cancers associated with poor outcomes and limited treatment options. There is currently no globally accepted standard of care in the second-line setting and chemotherapy as well as immunotherapies have demonstrated low response rates in BTC. Epithelial-to-mesenchymal transition (EMT), a hallmark of tumor progression and drug resistance, plays an important role in BTC, and has been shown to be triggered by TGF-β signaling.

About Bintrafusp Alfa

Bintrafusp alfa (M7824), discovered in-house at Merck, and currently in clinical development through a strategic alliance with GSK, is a potential first-in-class investigational bifunctional fusion protein designed to simultaneously block two immunosuppressive pathways, TGF-β and PD-L1, within the tumor microenvironment. This bifunctional approach is thought to control tumor growth by potentially restoring and enhancing anti-tumor responses. In preclinical studies, bintrafusp alfa has demonstrated antitumor activity both as monotherapy and in combination with chemotherapy. Based on its mechanism of action, bintrafusp alfa offers a potential targeted approach to addressing the underlying pathophysiology of difficult-to-treat cancers.

About the INTR@PID Clinical Trial Program

INTR@PID is a global clinical trial program investigating the potential co-localized, dual inhibition of TGF-β and PD-L1 with bintrafusp alfa (M7824) in multiple tumor types. Current clinical trial information can be found on the INTR@PID website at www.intrapidclinicaltrials.com. To date, globally more than 1,300 patients with various types of solid tumors have received bintrafusp alfa in the INTR@PID clinical development program.

The INTR@PID clinical development strategy is comprehensive and is pursuing non-redundant hypotheses grounded in preclinical and early clinical data findings that continue to be explored and may yield clinically meaningful insights to patients in need, including exploring settings where simultaneous, synchronized targeting of TGF-β and PD-L1 may offer the key to expanding the potential of immunotherapy; focusing on opportunities where PD-1/PD-L1 has suboptimal clinical activities and pathogenesis linked to TGF-β biology; and targeting specific tumors with biomarkers with a strong link to TGF-β signaling pathway.

All Merck Press Releases are distributed by e-mail at the same time they become available on the Merck Website. Please go to www.merckgroup.com/subscribe to register online, change your selection or discontinue this service.

On March 16, 2021 Elevation Oncology, a clinical stage biopharmaceutical company focused on the development of precision medicines for patients with genomically defined cancers, and NeoGenomics, Inc. (NASDAQ:NEO), a leading provider of cancer-focused genetic testing services and global oncology contract research services, reported a collaboration to enhance identification of patients with any solid tumor harboring an NRG1 fusion who may be eligible for enrollment in the Phase 2 CRESTONE study (Press release, Elevation Oncology, MAR 16, 2021, View Source;utm_medium=rss&utm_campaign=elevation-oncology-and-neogenomics-announce-collaboration-to-expand-genomic-testing-for-nrg1-fusions-across-solid-tumors-in-support-of-the-phase-2-crestone-study [SID1234576708]). NeoGenomics is a leading provider of next-generation sequencing (NGS) performing more than 50,000 NGS tests per year.

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NRG1 gene fusions are oncogenic driver alterations that have recently been identified in over 10 solid tumor types, with an overall estimated incidence of 0.2% in all solid tumors.1 Though rare, gene fusions are a proven target for precision oncology therapeutics, with over a dozen FDA-approved therapies now available for both hematologic and solid tumors driven by various gene fusions.2

"Our collaboration with Elevation Oncology reflects our shared pursuit of matching cancer patients to clinical trials and therapies that are precisely targeted to their unique tumor types and genomic biomarkers," said Douglas M. VanOort, Chairman and Chief Executive Officer of NeoGenomics. "Through cross-industry collaborations, we enable greater efficiency in the development and delivery of the latest advancements in both diagnostics and targeted therapies. Together, we work towards a future where every patient living with cancer has the opportunity to benefit from precision medicine."

As part of its comprehensive oncology test menu, NeoGenomics offers a variety of gene fusion panels that leverage RNA-based NGS to detect translocations and fusions with known and novel fusion partners across all solid tumors, including actionable gene fusions such as in ALK, BRAF, FGFR, NRG1, NTRK, PDGF, RET, and ROS1. In addition to all solid tumor panels, targeted panels are available in tumor types where gene fusions are commonly enriched:

Lung NGS Fusion Panel (Complete or Limited)
Cholangio/Pancreatic Carcinoma NGS Fusion Panel
Prostate NGS Fusion Panel
Thyroid NGS Fusion Panel
Targeted Solid Tumor NGS Fusion Panel
Universal Solid Tumor NGS Fusion Panel
RNA-based sequencing is the most sensitive detection method for structural variants that span large intronic regions, such as those leading to NRG1 gene fusions, which may not be detectable by most DNA-based sequencing techniques reliant on short-read methods. In addition, the use of RNA-based NGS furthers the scientific understanding of gene fusions by enabling full characterization of gene fusion partners and nucleotide-level resolution of fusion junctions.

"Accurate and widespread identification of gene fusions is critical to ensure patients can be matched to the growing number of approved and investigational precision therapies for these key oncogenic drivers," said Shawn Leland, PharmD, RPh, Founder and CEO of Elevation Oncology. "We are pleased to partner with NeoGenomics to ensure that across any solid tumor, each positive NRG1 fusion test result has the potential to be met with an actionable therapeutic opportunity in our Phase 2 CRESTONE study."

Patients and physicians can learn more about the CRESTONE study at www.nrg1fusion.com or on www.ClinicalTrials.gov under the NCT number NCT04383210.