On June 29, 2022 ReCode Therapeutics, a genetic medicines company using superior delivery to power the next wave of messenger RNA (mRNA) and gene correction therapeutics, reported the close of a Series B extension financing round, co-led by new investors, Leaps by Bayer, the impact investment unit of Bayer AG, AyurMaya, an affiliate of Matrix Capital Management, and with participation from Amgen Ventures (Press release, ReCode Therapeutics, JUN 29, 2022, View Source;utm_medium=rss&utm_campaign=recode-therapeutics-to-expand-next-generation-delivery-platform-and-diversify-genetic-medicines-pipeline-with-oversubscribed-series-b-financing-totaling-200m [SID1234619533]). With the additional $120M in new financing, the company has secured a total of $200M in Series B funding. In connection with the financing, Alan Colowick, M.D., M.P.H., managing director of Matrix, and Rakhshita Dhar, senior director of Venture investments Health at Leaps by Bayer, will join ReCode’s Board of Directors.

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"At AyurMaya, we help build companies that have the potential to transform the therapeutic landscape for patients. ReCode has an impressive combination of groundbreaking science, a highly accomplished leadership team and investor base, and the opportunity to have an immense impact on accelerating precision genetic medicines through delivery to disease-relevant cells," said Alan Colowick, M.D., M.P.H, Matrix Capital Management. "I am delighted to join ReCode’s Board during this important growth trajectory for the company and am eager to work with the leadership team to expand ReCode’s next generation genetic medicines delivery platform and diversify its pipeline."

The initial Series B financing announced in October 2021 was co-led by Pfizer Ventures and EcoR1 Capital and included Sanofi Ventures, Orbimed, Vida Ventures, MPM Capital, Colt Ventures, Hunt Technology Ventures L.P., Osage University Partners, Tekla Capital Management LLC, Superstring Capital, and NS Investment. Proceeds from the financing will be used to fund the diversification of ReCode’s pipeline into central nervous system (CNS), liver, and oncology indications, while continuing to advance ReCode’s lead mRNA programs for primary ciliary dyskinesia (PCD) and cystic fibrosis (CF) into the clinic. The funds also will be used to advance development of ReCode’s platform to deliver a wider range of genetic medicine cargoes, including additional gene correction modalities and small interfering RNA (siRNA) therapies, to a wider range of target cell types in a predictable and programmable fashion.

"The successful administration of billions of doses of mRNA COVID-19 vaccines, and continued progress with novel RNA and gene correction therapeutics, have catapulted us into a new era of possibility for genetic medicines. We are harnessing that potential with our novel selective organ targeting (SORT) lipid nanoparticle (LNP) delivery platform which is engineered with unique properties to enable delivery of genetic therapeutics directly to the organs and cells most impacted by disease, offering improved efficacy and potency. This potentially game-changing precision medicine technology creates vast possibilities for genetic medicines which have been limited by current technologies," said Shehnaaz Suliman, M.D., MBA, M.Phil., chief executive officer and board member, ReCode Therapeutics. "With the infusion of new capital and the addition of AyurMaya, an affiliate of Matrix Capital Management, and Leaps by Bayer to our high-caliber board, we are confident that our team will successfully drive ReCode’s mission to develop new precision genetic medicines enabled by superior delivery."

The capability to precisely target specific organs and cell types is important for maximizing the efficacy of genetic medicines and limiting potential adverse effects. Additionally, as evidenced with the mRNA COVID vaccines and novel RNA and gene correction therapeutics, LNP packaging enables redosing. For people with genetic diseases such as CF that require potentially lifelong therapy, this means LNP delivered therapeutics can be administered repeatedly over time, potentially without significant immunogenicity.

"The ability to directly target specific organs and cells beyond the liver remains a key challenge for genetic medicines," said Juergen Eckhardt, head of Leaps by Bayer. "At Leaps by Bayer, we strongly focus on finding breakthrough solutions that have the potential to make a meaningful difference for people with rare genetic diseases, and we believe ReCode is a unique company in our industry whose innovations have the potential to fundamentally shift an entire area of genetic medicine."

In May 2022, ReCode presented preclinical data from its two lead programs in PCD and CF at the American Thoracic Society (ATS) 2022 International Conference. These data demonstrated that selective organ targeting (SORT) LNP-formulated therapeutic candidates for PCD and CF can be precisely delivered directly to disease-relevant cells without significant exposure to other tissue, effectively releasing the encapsulated genetic cargo, and expressing the correct proteins at relevant levels. The company plans to advance to investigational new drug (IND) filings for PCD and CF in late 2022 and mid-2023, respectively.

About the SORT LNP Platform

ReCode is differentiated by its first-in-class modular genetic medicines delivery platform. The company’s selective organ targeting (SORT) lipid nanoparticle technology (LNP) platform is the foundation for its pipeline. Pioneered by co-founder Professor Daniel J. Siegwart, Ph.D., of the University of Texas, and described by Nature as one of the "Seven Technologies to Watch in 2022," ReCode’s SORT LNP platform is an innovation beyond the lipid delivery system used by the mRNA COVID vaccines and novel RNA and gene correction therapeutics.

LNPs are used to package and deliver genetic cargo such as mRNA. When delivered into the blood, first-generation LNPs primarily are taken up by the liver, which limits their utility for broad therapeutic applications. ReCode’s SORT LNPs are engineered with a biochemically distinct fifth lipid to help the body "sort" and direct the LNPs to other targeted organs such as the lung and spleen, with the ability to bypass the liver, if desired.

Beyond its highly selective targeting capability, ReCode’s SORT LNP platform is further distinguished by its versatility in both mode of administration (including IV, inhaled, subcutaneous, intramuscular, and intrathecal), and the diversity of genetic cargo that can be delivered (including mRNA, siRNA, DNA, gene correction components and mixed cargoes). Together, these qualities offer vast opportunities to address a wide range of unmet medical needs through a precision medicine approach that delivers the right medicine to the right organs and cells using the optimal mode of administration.

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.