On June 29, 2022 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported the launch of the BenchMark ULTRA PLUS system, its newest advanced tissue staining platform (Press release, Hoffmann-La Roche, JUN 29, 2022, View Source [SID1234616493]). The system enables quick and accurate test results so clinicians can make timely decisions regarding a patient’s care journey.

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"With the BenchMark ULTRA PLUS, we are pleased to offer an advanced tissue staining platform, co-developed with lab professionals," said Thomas Schinecker, CEO of Roche Diagnostics. "Waiting for a diagnosis is often one of the most stressful times for patients. This system enables pathologists to provide quick and accurate results that help inform patient treatment options."

Cancer and other abnormal cells can be characterised by biochemical markers from within the cells. By applying chemical solutions to tissue on glass slides with the BenchMark ULTRA PLUS, a healthcare professional can identify these markers to determine the presence or absence of key drivers that feed the unhealthy cells and, in many cases, the type of therapy that could be used to combat them.

The new BenchMark ULTRA PLUS system continues the evolution of the BenchMark series, which revolutionised cancer diagnostics by fully automating processes that used to be performed manually, one slide at a time.

Lab personnel will be able to manage their activities more efficiently as a result of simplified software and streamlined productivity and quality control. These enhancements can help support the quicker delivery of test results for patients who are waiting for a diagnosis.

The new system has several innovations such as new intuitive software, remote monitoring features, an integrated touchscreen for a more optimised user experience, and a more environmentally sustainable waste system and product packaging.

The BenchMark ULTRA PLUS system will be available to European Union countries in July 2022 and to the United States and in the Asia-Pacific market in September 2022, followed by a worldwide roll out in 2023.

About the BenchMark ULTRA PLUS system
The BenchMark ULTRA PLUS system (including hardware, software and assays) leverages the success of the current BenchMark series of IHC/ISH advanced staining platforms. It is built upon the proven technology of the BenchMark ULTRA system to deliver an enhanced lab experience. The BenchMark ULTRA PLUS system provides optimised workflow and flexible solutions, helping the anatomic pathology lab manage their activities efficiently and confidently, while selecting options that work best for their lab.

BenchMark ULTRA was the first advanced staining instrument to provide true, single-piece flow. BenchMark ULTRA PLUS pushes the envelope even further with its improved VENTANA System Software, which enhances quality control, inventory management and overall user experience due to its modern architecture. The BenchMark ULTRA PLUS incorporates several additional innovative features based on customer feedback, including remote monitoring with a connected device, new indicator lights, a retractable work surface, new slide drawers (that mitigate fluid ingress/egress), a new integrated touchscreen and more environmentally friendly waste segregation and degradation. Sustainable packaging uses 40% fewer raw materials and weighs less to provide a smaller carbon footprint while being transported. The system is manufactured using innovative and efficient assembly practices to ensure product quality and delivery.

On June 29, 2022, Athenex, Inc. (the "Company") reported that entered into the Fifth Amendment to Credit and Guaranty Agreement (the "Amendment") with Oaktree Fund Administration, LLC (as administrative agent for the Lenders, "Oaktree") and the other lenders party thereto (collectively, the "Lenders") (Filing, 8-K, Athenex, JUN 29, 2022, View Source [SID1234616448]). Under the Amendment, the Company agreed to make an additional prepayment in cash to the Lenders on or before July 1, 2022. This approximately $10.5 million prepayment consisted of (i) $10.0 million in principal amount; (ii) accrued and unpaid interest; and (iii) fees equal to 5.0% of the $10.0 million principal amount, allocated as a 2.0% Exit Fee and 3.0% Prepayment Fee (each as defined in the credit agreement).

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On June 29, 2022 Verrica Pharmaceuticals Inc. (Nasdaq: VRCA), a dermatology therapeutics company developing medications for skin diseases requiring medical interventions, reported that it intends to offer and sell, subject to market conditions, shares of its common stock in an underwritten public offering (Press release, Verrica Pharmaceuticals, JUN 29, 2022, View Source [SID1234616440]). All of the shares of common stock to be sold in the offering will be offered by Verrica. Verrica also intends to grant the underwriter a 30-day option to purchase up to an additional 15% of the shares of its common stock offered in the public offering on the same terms and conditions. The offering is subject to market conditions, and there can be no assurance as to whether or when the offering may be completed, or the actual size or terms of the offering.

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RBC Capital Markets is acting as sole book-runner for the offering.

A shelf registration statement relating to the shares of common stock offered in the public offering described above was filed with the Securities and Exchange Commission (SEC) on March 13, 2020 and declared effective by the SEC on March 25, 2020. The offering will be made only by means of a written prospectus and prospectus supplement that form a part of the registration statement. A preliminary prospectus supplement and accompanying prospectus relating to the offering will be filed with the SEC and will be available on the SEC’s website at www.sec.gov. Copies of the preliminary prospectus supplement and the accompanying prospectus, when available, may also be obtained by contacting RBC Capital Markets, Attention: Equity Capital Markets, 200 Vesey Street, 8th Floor, New York, NY 10281, or by telephone at (877) 822-4089 or by email at [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy the securities being offered, nor shall there be any sale of the securities being offered in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction.

On June 29, 2022 Celleron Therapeutics, the UK-based company developing innovative precision cancer medicines, reported a 3-year survival rate of 7.3% in late-stage micro-satellite stable colorectal cancer patients in their Phase II clinical trial, following treatment with zabadinostat (a potentially best-in-class HDAC inhibitor) and nivolumab (an immune checkpoint inhibitor commonly used to treat MSI CRC but has no activity in MSS CRC).

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The Phase II clinical trial (CAROSELL study) investigates the effect of zabadinostat (formerly CXD101) in combination with nivolumab in MSS colorectal cancer, which does not respond to immune checkpoint inhibitors (ICI) alone. The clinical strategy is well supported by scientific evidence showing how zabadinostat upregulates genes involved in antigen presentation and activity of natural killer cells, thus attracting cytotoxic T-cells to tumours and killing cells through the immune system; in essence, "turning cold tumours hot".

Following a dose confirmation safety run-in, which showed no treatment-induced toxicity, a Phase II recommended dose (P2RD) of zabadinostat and nivolumab was selected for further investigation. The patients in the study had advanced or metastatic disease, having relapsed after at least two previous lines of therapy.

Enrolment to the Phase II study was completed in May 2019, and all ongoing subjects have completed study treatment. Of 46 evaluable MSS CRC subjects, 22 (48%) exhibited durable disease control (stable disease plus partial response).

Post-treatment survival analysis is still ongoing, with surviving patients now under standard of care. The median Overall Survival (OS) was 7 months. Of all patients treated, 8/55 (14.5%) remained in survival 2 years from first dose. To date, 4/55 (7.3%) patients continue to survive past the three-year follow-up point.

Safety wise, the study combination was well tolerated. The most frequent observed Adverse Events were fatigue, nausea, and cytopenia. All AEs were manageable. There were no deaths or discontinuations from the study due to adverse drug reactions.

In consideration to the mechanism of action, clinical activity and safety, the results in this Phase II study suggest that zabadinostat plus nivolumab may be a superior treatment in advanced MSS CRC than marketed products, such as Lonsurf and Stivarga.

David Kerr, CMO of Celleron Therapeutics and Professor of Cancer Medicine at the University of Oxford, commented:

"We are pleased to continue seeing evidence that zabadinostat and nivolumab may prolong survival in very late-stage cancer patients, with some surviving past three years, the significance of which cannot be understated. This Phase II study not only strengthens the argument that zabadinostat is a clinically viable drug, but perhaps also the best-in-class treatment for cold tumours, such as MSS CRC which do not respond to treatment with immune checkpoint drugs. We remain dedicated to deploying zabadinostat as a precision medicine, maximising clinical benefit by using immune biomarkers to improve selection of patients – a key deliverable of our upcoming Phase III study".

NOTES:
About Colorectal Cancer

Colorectal cancer is the second most common tumour type in women, and the third most common in men, globally. The approximate 5-year survival rate for colorectal cancer patients in the United States is 10% for those with advanced metastatic disease (Stage IV).

Surgery is indicated for localised disease, whilst chemotherapy has been the standard management for patients with metastatic colorectal cancer. Two agents have been approved for third line management of advanced colorectal cancer, namely regorafenib and Trifluridine-tipiracil hydrochloride (Lonsurf).

A subset (5%) of colorectal cancers is characterized with deficient DNA mismatch repair (dMMR or microsatellite instability, MSI). These tumours tend to have a high expression of checkpoint proteins (PD-1 and PD-L1), which interfere with the body’s normal anti-tumour T-cell response. By disabling these proteins, immune checkpoint inhibitors (ICI) such as nivolumab allow the immune system to function properly, and T-cells to kill tumour cells.

However, for the greater majority of patients with a normal Mismatch Repair proficient expression, the microsatellite phenotype is stable (MSS), antigen presentation is believed to be much decreased, and the tumour is thus resistant to checkpoint inhibition. Most MSS patients will ultimately relapse or become resistant to chemotherapy. Thus, there remains a very significant unmet clinical need to find novel agents, singly and/or in combination, for the treatment of these late-stage patients.

On June 29, 2022 Cytokinetics, Incorporated ("Cytokinetics") (Nasdaq: CYTK) reported its intention to offer, subject to market and other conditions, $450.0 million aggregate principal amount of convertible senior notes due 2027 (the "notes") in a private offering to qualified institutional buyers pursuant to Rule 144A under the Securities Act of 1933, as amended (the "Securities Act") (Press release, Cytokinetics, JUN 29, 2022, View Source [SID1234616412]). Cytokinetics also expects to grant the initial purchasers of the notes an option to purchase, for settlement within a period of 13 days from, and including, the date the notes are first issued, up to an additional $90.0 million aggregate principal amount of notes.

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The notes will be senior, unsecured obligations of Cytokinetics and will accrue interest payable semi-annually in arrears. The notes will mature on July 1, 2027, unless earlier converted, redeemed or repurchased by Cytokinetics. Noteholders will have the right to convert their notes in certain circumstances and during specified periods. Cytokinetics will settle conversions by paying or delivering, as applicable, cash, shares of its common stock or a combination of cash and shares of its common stock, at Cytokinetics’ election. The notes will be redeemable, in whole or in part (subject to certain limitations), at Cytokinetics’ option at any time, and from time to time, on or after July 6, 2025 and, in the case of any partial redemption, on or before the 60th scheduled trading day immediately before the maturity date, at a cash redemption price equal to the principal amount of the notes to be redeemed, plus accrued and unpaid interest, if any, to, but excluding, the redemption date, but only if the last reported sale price per share of Cytokinetics’ common stock exceeds 130% of the conversion price for a specified period of time. The interest rate, initial conversion rate and other terms of the notes will be determined at the pricing of the offering.

Cytokinetics intends to use a portion of the net proceeds from the offering and to issue shares of its common stock to repurchase a portion of its outstanding 4.00% convertible senior notes due 2026 (the "2026 notes") through privately negotiated transactions entered into concurrently with the pricing of the offering. The terms of any repurchases of the 2026 notes will depend on factors, including the market price of Cytokinetics’ common stock and the trading price of the 2026 notes at the time of such repurchases.

Cytokinetics intends to use the remainder of the net proceeds of this offering to (a) expand and support its clinical development program for aficamten in patients with hypertrophic cardiomyopathy ("HCM"), including the spending associated with the potential conduct of a second Phase 3 clinical trial in patients with obstructive HCM and a first Phase 3 clinical trial in patients with non-obstructive HCM; (b) expand commercial capabilities and conduct readiness activities in the United States, Canada and Europe to support the potential launch of omecamtiv mecarbil and aficamten in those geographies; (c) advance its early stage clinical development pipeline, including the progression of CK-136 to proof of concept studies and the potential development of additional cardiac myosin inhibitors for the potential treatment of heart failure with preserved ejection fraction ("HFpEF"); (d) expand its muscle biology focused research activities to energetics, growth and metabolism of muscle, and (e) for general corporate purposes, including working capital.

In connection with any repurchase of the 2026 notes, Cytokinetics expects that holders of the outstanding 2026 notes that have hedged their equity price risk with respect to the 2026 notes (the "hedged holders") will, concurrently with the pricing of the notes, unwind their hedge positions by buying Cytokinetics’ common stock and/or entering into or unwinding various derivative transactions with respect to its common stock. The amount of common stock to be purchased by the hedged holders may be substantial in relation to the historic average daily trading volume of Cytokinetics’ common stock. This activity by the hedged holders may increase the effective conversion price of the notes.

The offer and sale of the notes and any shares of common stock issuable upon conversion of the notes have not been, and will not be, registered under the Securities Act or any other securities laws, and the notes and any such shares may not be offered or sold except pursuant to an exemption from, or in a transaction not subject to, the registration requirements of the Securities Act and any other applicable securities laws.

This press release does not constitute an offer to sell, or the solicitation of an offer to buy, the notes or any shares of common stock issuable upon conversion of the notes, nor will there be any sale of the notes or any such shares, in any state or other jurisdiction in which such offer, sale or solicitation would be unlawful.