Silence Therapeutics Appoints Mark Rothera as President and Chief Executive Officer

On September 15, 2020 Silence Therapeutics plc, AIM:SLN and Nasdaq: SLN ("Silence" or "the Company"), a leader in the discovery, development and delivery of novel short interfering ribonucleic acid (siRNA) therapeutics for the treatment of diseases with significant unmet medical need, reported the appointment of Mark Rothera as President and Chief Executive Officer (CEO) and Board member, effective immediately (Press release, Silence Therapeutics, SEP 15, 2020, View Source [SID1234565163]). Iain Ross, who has been Executive Chairman since December 2019, has today assumed his previous position of Non-Executive Chairman.

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Mr. Rothera brings more than 30 years of experience in the biopharmaceutical industry, with a strong record of commercial and operational leadership, including driving the successful build of multiple biotech companies, predominantly in the field of rare or specialty diseases.

Prior to joining Silence, Mr. Rothera served as CEO of Orchard Therapeutics (Orchard), where he oversaw its transformation from a small U.K.-based, privately held company with two clinical-stage programmes into a leading gene therapy company with seven clinical-stage programmes and fully integrated capabilities. Under his leadership, Orchard completed an initial public offering of American Depositary Shares on the Nasdaq Global Market and during his tenure that company secured more than $600 million in financing and grew from a market capitalization of $250 million to more than $1.7 billion at its peak. Prior to Orchard, Mr. Rothera served as Chief Commercial Officer of PTC Therapeutics (PTC), where he helped transition that company from a privately held R&D biotechnology company to a publicly traded, commercial-stage company with a global footprint, including the successful launch of two rare disease therapies. He also previously served as Global President of Aegerion Pharmaceuticals Inc. and Vice President and General Manager of commercial operations at Shire Human Genetic Therapies for Europe, Middle East and Africa. Mr. Rothera received an M.A. in Natural Sciences from Cambridge University and an M.B.A. from the European Institute for Business Administration (INSEAD).

Based out of Silence’s New York City office, Mr. Rothera will lead the continued global expansion of the Company. His appointment follows the completion of Silence’s Nasdaq listing on 8 September 2020 and aligns with the strategy of increasing the Company’s presence in the United States.

Iain Ross, Chairman of Silence Therapeutics plc, said: "On behalf of the Silence Board and the entire Silence team, I welcome Mark to the Company. Following a thorough search, Mark’s appointment reflects his proven leadership skills and strong track record in growing successful biotechnology companies and building shareholder value. I believe he will now provide the leadership necessary to grow Silence into a leading international biotechnology company built upon our innovative siRNA technology platform, proprietary product pipeline and validating industry partnerships.

"On a personal note, and on behalf of the Board, I would like to thank the management team and staff at Silence for theirsupport, hard work and tremendous resilience during the current COVID-19 pandemic and over the past nine months whilst I have been Executive Chairman. The Company has made great strides during this period, and is now in a strong position, both operationally and financially, and ready for Mark to take the helm.

" Mark Rothera, President and CEO of Silence Therapeutics plc, added: "It is an honour to take the role of leading Silence at this time in the Company’s history. I believe the Company is poised to capitalise on its important siRNA technology platform, pipeline and research capabilities built over 18 years, and position itself as a leader in the RNAi field. The Company has made great strides under Iain’s leadership and I look forward to working with the Board, the management team and Silence employees to build upon this momentum."

AVEO Oncology Announces European Urology Publication of Final Overall Survival Data from Phase 3 TIVO-3 Study of Tivozanib in Renal Cell Carcinoma

On September 15, 2020 AVEO Oncology (Nasdaq: AVEO) reported that final overall survival (OS) results from its Phase 3 TIVO-3 study were published in the journal European Urology (Press release, AVEO, SEP 15, 2020, View Source [SID1234565192]). TIVO-3 is the Company’s pivotal Phase 3 trial comparing tivozanib, AVEO’s next-generation vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor (TKI) drug candidate, to sorafenib in third and fourth line renal cell carcinoma (RCC) . The article, titled "Final Overall Survival Results from a Phase 3 Study to Compare Tivozanib to Sorafenib as Third- or Fourth-line Therapy in Subjects with Metastatic Renal Cell Carcinoma," is available online first via this link.

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"TIVO-3 represents the first positive superiority study in the growing population of patients who have relapsed or become refractory to multiple lines of therapy, including checkpoint inhibitors," said Sumanta (Monty) Pal, MD, Associate Clinical Professor, Department of Medical Oncology and Therapeutics Research, and Co-director, Kidney Cancer Program, at City of Hope Comprehensive Cancer Center, and lead author. "TIVO-3 data suggest a favorable safety and efficacy profile relative to sorafenib as demonstrated by superior anti-tumor progression free survival and overall response activity vs. another VEGFR TKI, coupled with fewer dose reductions, interruptions and discontinuations. The OS hazard ratio (HR) is consistent with previous Phase 3 studies comparing two VEGF-directed agents. I believe that tivozanib has the potential to offer patients a meaningful new treatment option in a setting currently lacking an evidence-based standard of care."

"For RCC patients who have relapsed or are refractory to multiple lines of therapy, the lack of well controlled clinical data to guide treatment decisions in this advanced relapsed/refractory population poses challenges for patients and treating physicians," said Michael Bailey, president and chief executive officer of AVEO. "We expect that Tivozanib’s TIVO-3 data has the potential to guide important treatment decisions in this setting and ultimately improve outcomes and patient experience. We look forward to working with the U.S. Food and Drug Administration (FDA) as they continue to review our New Drug Application (NDA) submission."

In June 2020, AVEO announced that the FDA accepted for filing its NDA seeking approval for tivozanib as a treatment for relapsed or refractory RCC. The FDA has assigned the application standard review and a Prescription Drug User Fee Act target action date of March 31, 2021. The FDA also indicated that they do not currently plan on convening an Oncologic Drug Advisory Committee (ODAC) to discuss the application. The NDA submission is based on the TIVO-3 study and is also supported by three additional trials in RCC and includes safety data from over 1,000 clinical trial subjects and several years of commercial availability in Europe.

Results in Detail

Patients enrolled in the TIVO-3 trial (n=350) were randomized and stratified by prior regimen and IMDC prognostic score. Prior treatment regimens included prior checkpoint inhibitor and VEGF TKI therapies (n=91), two prior VEGF TKI therapies (n=159) and prior VEGF TKI and other therapies (n=100). As previously announced, the TIVO-3 trial met the primary endpoint of progression free survival (PFS), with a median PFS of 5.6 months in the tivozanib arm vs. 3.9 months in the sorafenib arm (HR=0.73; p=0.02), and the secondary endpoint of overall response rate (ORR) (18% vs. 8%; p=0.02).

For the secondary endpoint of OS, the OS HR, which assesses the overall relative risk of death, was 0.97 (95% CI: 0.75-1.24; p=0.82), favoring tivozanib and improving from the previously reported interim HR of 0.99. Median OS, representing a single point in time in the OS curve, was 16.4 months for tivozanib (95% CI: 13.4-22.2) and 19.2 months for sorafenib (95% CI: 15.0-24.2). These OS HR results are similar to those of prior VEGFR TKI vs. VEGFR TKI studies in RCC.1-4

Tivozanib was found to be generally well-tolerated, with grade 3 or higher adverse events (AEs) consistent with those observed in previous tivozanib trials. The most common AE in patients receiving tivozanib was hypertension (38% vs. 25% for sorafenib, of treated patients), an AE known to reflect effective VEGF pathway inhibition. Infrequent but severe AEs reported in greater number in the tivozanib arm were thrombotic events (5% vs. 4% for sorafenib, of treated patients) similar to those observed in previous tivozanib studies. Dose reductions and interruptions due to AEs were significantly lower for tivozanib vs. sorafenib, despite nearly double the average number of cycles initiated for the tivozanib arm (11.9 months vs. 6.7 months for sorafenib), and treatment related AEs leading to permanent discontinuation were 8% for tivozanib vs. 15% for sorafenib.

About Tivozanib (FOTIVDA)

Tivozanib is an oral, once-daily, next-generation vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) discovered by Kyowa Kirin and approved as FOTIVDA for the treatment of adult patients with advanced renal cell carcinoma (RCC) in the European Union and other countries in the EUSA territory. It is a potent, selective and long half-life inhibitor of all three VEGF receptors and is designed to optimize VEGF blockade while minimizing off-target toxicities, potentially resulting in improved efficacy and minimal dose modifications.5,6 Tivozanib is being studied in the TIVO-3 trial, which is supporting a regulatory submission of tivozanib in the U.S. seeking marketing approval as a treatment for relapsed or refractory RCC. Tivozanib has been shown to significantly reduce regulatory T-cell production in preclinical models7 and has demonstrated synergy in combination with nivolumab (anti PD-1) in a Phase 2 study in RCC.8 Tivozanib has been investigated in several tumor types, including renal cell, hepatocellular, colorectal, ovarian and breast cancers. Tivozanib is also being studied by partner Kyowa Kirin in non-oncology indications.

Entry into a Material Definitive Agreement.

On September 15, 2020 CNS Pharmaceuticals, Inc. (the "Company") reported that it entered into a purchase agreement (the "Purchase Agreement"), and a registration rights agreement (the "Registration Rights Agreement"), with Lincoln Park Capital Fund, LLC ("Lincoln Park"), pursuant to which Lincoln Park has committed to purchase up to $15.0 million worth of the Company’s common stock, $0.001 par value per share (the "Common Stock") (Filing, 8-K, CNS Pharmaceuticals, SEP 15, 2020, View Source [SID1234565417]).

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Under the terms and subject to the conditions of the Purchase Agreement, the Company has the right, but not the obligation, to sell to Lincoln Park, and Lincoln Park is obligated to purchase up to $15.0 million worth of shares of the Company’s Common Stock. Such sales of Common Stock by the Company, if any, will be subject to certain limitations, and may occur from time to time, at the Company’s sole discretion, over the 36-month period commencing on the date that a registration statement covering the resale of shares of Common Stock that have been and may be issued under the Purchase Agreement, which the Company agreed to file with the Securities and Exchange Commission (the "SEC") pursuant to the Registration Rights Agreement, is declared effective by the SEC and a final prospectus in connection therewith is filed and the other conditions set forth in the purchase agreement are satisfied, all of which are outside the control of Lincoln Park (such date on which all of such conditions are satisfied, the "Commencement Date").

Thereafter, under the Purchase Agreement, on any business day selected by the Company that the closing sale price of the Common Stock equals or exceeds the threshold price set forth in the Purchase Agreement, the Company may direct LPC to purchase up to 30,000 shares of Company Common Stock on such business day (each, a "Regular Purchase"), provided, however, that (i) the Regular Purchase may be increased to up to 50,000 shares, provided that the closing sale price of the Common Stock is not below $2.00 on the purchase date; (ii) the Regular Purchase may be increased to up to 75,000 shares, provided that the closing sale price of the Common Stock is not below $2.50 on the purchase date; (iii) the Regular Purchase may be increased to up to 100,000 shares, provided that the closing sale price of the Common Stock is not below $3.00 on the purchase date; and (iv) the Regular Purchase may be increased to up to 150,000 shares, provided that the closing sale price of the Common Stock is not below $4.00 on the purchase date. In each case, Lincoln Park’s maximum commitment in any single Regular Purchase may not exceed $1,000,000. In addition, after the Commencement Date, the Company may direct Lincoln Park to purchase, on two separate occasions that must be at least 30 business days apart, $1,000,000 worth of Common Stock per such purchase (each, a "Tranche Purchase"). The purchase price per share for each Regular Purchase and each Tranche Purchase will be based on prevailing market prices of the Common Stock immediately preceding the time of sale. There are no upper limits on the price per share that Lincoln Park must pay for shares of Common Stock under the Purchase Agreement. In addition to Regular Purchases and Tranche Purchases, the Company may also direct Lincoln Park to purchase other amounts as accelerated purchases or as additional accelerated purchases if the closing sale price of the Common Stock equals or exceeds the threshold price at the times set forth in the Purchase Agreement. The above-referenced share amount limitations and closing sale price thresholds are subject to adjustment for any reorganization, recapitalization, non-cash dividend, stock split, reverse stock split or other similar transaction as provided in the Purchase Agreement.

Lincoln Park has no right to require the Company to sell any shares of Common Stock to Lincoln Park, but Lincoln Park is obligated to make purchases as the Company directs, subject to satisfaction of the conditions set forth in the Purchase Agreement. Actual sales of shares of Common Stock to Lincoln Park will depend on a variety of factors to be determined by the Company from time to time, including, among others, market conditions, the trading price of the Common Stock and determinations by the Company as to the appropriate sources of funding for the Company and its operations.

The net proceeds under the purchase agreement to the Company will depend on the frequency and prices at which the Company sells shares of its stock to Lincoln Park. The Company expects that any proceeds received by the Company from such sales to Lincoln Park will be used for working capital and general corporate purposes.

The aggregate number of shares that the Company can sell to Lincoln Park under the Purchase Agreement may in no case exceed 19.99% of the shares of the Common Stock outstanding immediately prior to the execution of the Purchase Agreement) (the "Exchange Cap"), unless (i) stockholder approval is obtained to issue shares above the Exchange Cap, in which case the Exchange Cap will no longer apply, or (ii) the average price of all applicable sales of our Common Stock to Lincoln Park under the Purchase Agreement equals or exceeds the lower of (A) the official closing price of the Company’s Common Stock on Nasdaq on the trading day immediately preceding the date of the Purchase Agreement and (B) the average official closing price of our Common Stock on Nasdaq for the five consecutive trading days ending on the trading day immediately preceding the date of the Purchase Agreement, adjusted such that the transactions contemplated by the Purchase Agreement are exempt from the Exchange Cap limitation under applicable Nasdaq rules.

In all instances, the Company may not sell shares of its Common Stock to Lincoln Park under the purchase agreement if it would result in Lincoln Park beneficially owning more than 4.99% of its Common Stock.

The Company has agreed with Lincoln Park that it will not enter into any "variable rate" transactions as defined in the Purchase Agreement with any third party for a period set forth in the Purchase Agreement. Lincoln Park has covenanted not to cause or engage in any manner whatsoever, any direct or indirect short selling or hedging of the Common Stock.

As consideration for Lincoln Park’s irrevocable commitment to purchase Common Stock upon the terms of and subject to satisfaction of the conditions set forth in the Purchase Agreement, upon execution of the Purchase Agreement, the Company issued 201,991 shares of Common Stock to Lincoln Park as commitment shares.

Lincoln Park has represented to the Company, among other things, that it is an "accredited investor" (as such term is defined in Rule 501(a) of Regulation D under the Securities Act of 1933, as amended (the "Securities Act")). The securities referred to in this current report on Form 8-K are being issued and sold by the Company to Lincoln Park in reliance upon the exemptions from the registration requirements of the Securities Act afforded by Section 4(a)(2) of the Securities Act and Rule 506(b) of Regulation D promulgated thereunder.

The Purchase Agreement and the Registration Rights Agreement contain customary representations, warranties, agreements and conditions to completing future sale transactions, indemnification rights and obligations of the parties. The Company has the right to terminate the Purchase Agreement at any time, at no cost or penalty. During any "event of default" under the Purchase Agreement, all of which are outside of Lincoln Park’s control. The Company may not initiate any regular or other purchase of shares by Lincoln Park, until an event of default is cured. In addition, in the event of bankruptcy proceedings by or against the Company, the purchase agreement will automatically terminate.

This current report on Form 8-K shall not constitute an offer to sell or a solicitation of an offer to buy any shares of Common Stock, nor shall there be any sale of shares of Common Stock in any state or jurisdiction in which such an offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or other jurisdiction.

The foregoing descriptions of the Purchase Agreement and the Registration Rights Agreement are qualified in their entirety by reference to the full text of such agreements, copies of which are attached hereto as Exhibit 10.1 and 10.2, respectively, and each of which is incorporated herein in its entirety by reference. The representations, warranties and covenants contained in such agreements were made only for purposes of such agreements and as of specific dates, were solely for the benefit of the parties to such agreements, and may be subject to limitations agreed upon by the contracting parties.

GSK highlights scientific advances across its growing oncology portfolio at ESMO Virtual Congress 2020

On September 15, 2020 GlaxoSmithKline plc reported that it will present new data at the upcoming European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Virtual Congress 2020, underscoring its commitment to advancing its growing oncology portfolio, which includes the recent European Commission (EC) and US Food and Drug Administration (FDA) approvals of BLENREP (belantamab mafodotin) for patients with relapsed/refractory multiple myeloma, and the FDA approval of a new indication in first-line ovarian cancer for ZEJULA (niraparib) (Press release, GlaxoSmithKline, SEP 15, 2020, View Source [SID1234565139]).

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Reflecting the increasing depth and breadth of GSK’s innovative research in oncology, investigators will present 13 abstracts covering a range of approved and investigational therapies, focused on science related to the immune system, the use of human genetics and other research platforms.

GSK presentations at ESMO (Free ESMO Whitepaper) will focus on research intended to improve outcomes for women with high unmet medical needs, including data related to the safety and efficacy of ZEJULA in patients with advanced, recurrent or resistant ovarian cancer. Investigators also will present a late-breaking presentation: "Safety and Antitumor Activity of Dostarlimab in Patients (Pts) with Advanced or Recurrent DNA Mismatch Repair Deficient (dMMR) or Proficient (MMRp) Endometrial Cancer (EC): Results from GARNET."

Dr Axel Hoos, Senior Vice President and Head of Oncology R&D, GSK said: "This year we have achieved strong momentum for our oncology pipeline, with 14 assets in clinical development across four key research areas. Recent approvals for BLENREP in multiple myeloma and a new indication for ZEJULA in first-line ovarian cancer have delivered new treatment options for patients with unmet needs, and we look forward to sharing new data from our oncology pipeline at ESMO (Free ESMO Whitepaper)."

A list of additional presentations focused on GSK therapies at ESMO (Free ESMO Whitepaper) can be found below:

Synthetic Lethality

Abstract Name

Presenter

Presentation Details

Patient-Reported Outcomes (PRO) in Patients (Pts) Receiving Niraparib in the PRIMA/ENGOT-OV26/GOG-3012 Trial

Pothuri, B.

810MO

Efficacy and Safety of Niraparib in Older Patients (Pts) with Advanced Ovarian Cancer (OC): Results from the PRIMA/ENGOT-OV26/GOG-3012 Trial

Valabrega, G.

819P

MOONSTONE/GOG-3032: A Phase II, Open-Label, Single-Arm Study to Evaluate the Efficacy and Safety of Niraparib + Dostarlimab in Patients with Platinum-Resistant Ovarian Cancer

Randall, L.M.

883TiP

JASPER: Efficacy and Safety of First-Line (1L) Niraparib Plus a Programmed Death Receptor 1 Inhibitor (PD-1i) in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)

Ramalingam, S.S.

1268P

Immuno-oncology

Abstract Name

Presenter

Presentation Details

Safety and Efficacy of Dostarlimab in Patients (Pts) with Recurrent/Advanced Non-Small Cell Lung Cancer (NSCLC)

Subramanian, J.

1399P

Patient-Reported Outcomes (PROs) in the GARNET Trial in Patients (Pts) with Advanced or Recurrent Mismatch Repair Deficient/Microsatelite Instability-High (dMMR/MSI-H) Endometrial Cancer (EC) Treated with Dostarlimab

Kristeleit, R.

858P

The Relationship Between Overall Survival (OS), Progression-Free Survival (PFS), and Objective Response Rate (ORR) in Immune Checkpoint Inhibitor Clinical Trials of Head and Neck Squamous Cell Carcinoma (HNSCC): A Systematic Review and Meta-analysis

Wang, X.

951P

Matching-Adjusted Indirect Comparisons (MAIC) of Safety Between Single-Agent Belantamab Mafodotin Versus Selinexor Plus Dexamethasone in Relapsed/Refractory Multiple Myeloma (RRMM)

· Suvannasankha, A.

901P

A Phase II/III, Randomized, Placebo-Controlled Study of Bintrafusp Alfa with Gemcitabine Plus Cisplatin as First-Line Treatment of Biliary Tract Cancer

Oh, D-Y.

79TiP

Long-Term Follow-Up of Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGF-β and PD-L1, in Patients with Pretreated Biliary Tract Cancer

Yoo, C.

73P

Three-Year Follow-up of Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGF-β and PD-L1, for Second-Line (2L) Treatment of Advanced Non-Small Cell Lung Cancer (NSCLC)

Paz-Ares, L.

1272P

Phase 2 Study of Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGF-β and PD-L1, in Platinum-Experienced Advanced Cervical Cancer

Birrer, M.

879TiP

GSK in Oncology

GSK is focused on maximising patient survival through transformational medicines. GSK’s pipeline is focused on immuno-oncology, cell therapy, cancer epigenetics and synthetic lethality. Our goal is to achieve a sustainable flow of new treatments based on a diversified portfolio of investigational medicines utilising modalities such as small molecules, antibodies, antibody-drug conjugates and cell therapy, either alone or in combination.

Axial Biotherapeutics to Present at the H.C. Wainwright 22nd Annual Global Investment Conference

On September 15, 2020 Axial Biotherapeutics, a biotechnology company dedicated to building a unique class of gut-targeted programs for neurodegenerative diseases and neurodevelopmental disorders, reported that management will present at the H.C. Wainwright Annual Global Investment Conference on Tuesday, September 15, 2020 at 2:00 PM ET (Press release, Axial Biotherapeutics, SEP 15, 2020, https://www.axialbiotherapeutics.com/2020/09/axial-biotherapeutics-to-present-at-the-h-c-wainwright-22nd-annual-global-investment-conference/ [SID1234565165]).

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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