On November 30, 2022 The Menarini Group ("Menarini"), a privately held Italian pharmaceutical and diagnostics company, and Stemline Therapeutics ("Stemline"), a wholly-owned subsidiary of the Menarini Group, will present additional data from the Phase 3 EMERALD study (NCT03778931) of elacestrant, an investigational oral SERD, during the upcoming San Antonio Breast Cancer Symposium (SABCS) being held from December 6-10 (Press release, Menarini, NOV 30, 2022, View Source;in-metast-301690442.html [SID1234624624]).

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EMERALD is a Phase 3 registrational trial that demonstrated statistically significant progression-free survival (PFS) with elacestrant vs SOC endocrine monotherapy (fulvestrant, letrozole, anastrozole, exemestane), meeting both primary endpoints in all patients and in those patients harbouring ESR1 mutations (ESR1-mut), following progression on prior CDK4/6 inhibitors (CDK4/6i) in ER+, HER2- advanced or metastatic breast cancer.

A post-hoc analysis of the PFS results in the EMERALD trial based on the duration of prior CDK4/6i usage shows clinically meaningful results which favor monotherapy elacestrant, both in the total patient population as well as in patients with ESR1-mut. Increased duration of prior CDK4/6i in metastatic patients was positively associated with longer PFS on elacestrant but not with SOC.

For those who were exposed to CDK4/6i ≥12 months prior to randomization on EMERALD, elacestrant achieved:

In the all-patient population, a mPFS of 3.8 months on elacestrant vs 1.9 months on SOC, a 39% reduction in the risk of progression or death (HR=0.61 95% CI: 0.45-0.83)
In the ESR1-mut population, a mPFS of 8.6 months on elacestrant vs 1.9 months on SOC, a 59% reduction in the risk of progression or death (HR=0.41 95% CI: 0.26-0.63)
For those who were exposed with CDK4/6i ≥18 months prior to randomization on EMERALD, elacestrant achieved:

In the all-patient population, a mPFS of 5.5 months on elacestrant vs 3.3 months with SOC, a 30% reduction in the risk of progression or death (HR=0.70 95% CI: 0.48-1.02)
In the ESR1-mut population, a mPFS of 8.6 months on elacestrant vs 2.1 months on SOC, a 53% reduction in the risk of progression or death (HR=0.47 CI: 0.20-0.79).
Updated safety data were consistent with previously reported results. Most of the adverse events (AEs), including nausea, were grade 1 and 2, and only 3.4% and 0.9% of the patients discontinued trial therapy because of an AE on elacestrant and SOC, respectively. A low percentage of patients received an antiemetic; 8.0% on elacestrant, 3.7% on fulvestrant, and 10.3% on AI, respectively. No hematological safety signal was observed and none of the patients in either of the two treatment arms had sinus bradycardia.

Virginia Kaklamani, MD, DSc, breast medical oncologist and professor of medicine, UT Health San Antonio, MD Anderson Cancer Center, commented, "These results show that when used as a single agent, elacestrant provided mPFS up to 8.6 months, based on the duration of previous CDK4/6 inhibitor therapy, with a manageable safety profile and the convenience of an oral tablet. This suggests elacestrant may have the potential to become a new standard of care as a monotherapy endocrine sequencing option in ER+, HER2- advanced breast cancer after progression on CDK4/6i, before moving to combination therapies."

"These results further highlight elacestrant’s potential to change the treatment paradigm of ER+, HER2- advanced or metastatic breast cancer. Elacestrant is under Priority Review with the U.S. Food and Drug Administration (FDA) with a target PDUFA date of February 17, 2023," commented Elcin Barker Ergun, Chief Executive Officer of the Menarini Group.

A complete list of key Menarini Group presentations at SABCS is below.

Lead Author Name

Abstract Number and Title

Presentation Details

V. Kaklamani

GS3-01. EMERALD Phase 3 trial of elacestrant versus standard of care endocrine therapy in patients with ER+, HER2- metastatic breast cancer: Updated results by duration of prior CDK4/6i in metastatic setting

December 8, 2022

8:30-8:45 AM CT

Oral Presentation

General Session 3

Hall 3

H. Rugo

OT2-01-03. ELEVATE: A Phase 1b/2, open-label, umbrella study evaluating elacestrant in various combinations in women and men with metastatic breast cancer (mBC)

December 7, 2022

5:00-6:30 PM CT

Ongoing Trials Poster Session 2

Hall 1

M. Piccart

PD18-05. MEN1611, a PI3K Inhibitor, combined with trastuzumab (T) ± fulvestrant (F) for HER2+/PIK3CA mutant (mut) advanced or metastatic (a/m) breast cancer (BC): updated safety and efficacy results from the ongoing Phase 1b study (B-PRECISE-01)

December 9, 2022

7:00-8:15 AM CT

Spotlight Poster Discussion 18

Stars at Night Ballroom – Hall 3&4

The Menarini Group obtained global licensing rights for elacestrant in July 2020 from Radius Health, Inc., who conducted and successfully completed the EMERALD study. The Menarini Group is now fully responsible for global registration, commercialization, and further development activities for elacestrant.

About Elacestrant (RAD1901) and the EMERALD Phase 3 Study

Elacestrant is an investigational selective estrogen receptor degrader (SERD). In 2018, elacestrant received Fast Track designation from the FDA. Preclinical studies completed prior to EMERALD indicate that the compound has the potential for use as a single agent or in combination with other therapies for the treatment of breast cancer. The EMERALD Phase 3 trial is a randomized, open label, active-controlled study evaluating elacestrant as second- or third-line monotherapy in ER+, HER2- advanced/metastatic breast cancer patients. The study enrolled 478 patients who had received prior treatment with one or two lines of endocrine therapy, including a CDK 4/6 inhibitor. Patients in the study were randomized to receive either elacestrant or the investigator’s choice of an approved hormonal agent. The primary endpoints of the study were progression-free survival (PFS) in the overall patient population and in patients with estrogen receptor 1 gene (ESR1) mutations. Secondary endpoints included evaluation of overall survival (OS), objective response rate (ORR), and duration of response (DOR) and safety.

On November 30, 2022 TC BioPharm (Holdings) PLC ("TC BioPharm" or the "Company") (Nasdaq: TCBP) (Nasdaq: TCBPW), a clinical stage biotechnology company developing platform allogeneic gamma-delta T cell therapies for cancer treatment, reported the closing of its previously announced private placement for the issuance and sale of 1,470,000 American Depositary Shares (the "ADSs")(or ADS equivalents in lieu thereof), Series A warrants to purchase up to an aggregate of 1,470,000 ADSs and Series B warrants to purchase up to an aggregate of 1,470,000 ADSs at a purchase price of $5.00 per ADS (or ADS equivalent in lieu thereof) and associated warrants (Press release, TC Biopharm, NOV 30, 2022, View Source [SID1234624623]). Each ADS representing one ordinary share of the Company. The Series A warrants are exercisable immediately upon issuance at an exercise price of $5.00 per ADS and will expire five and one-half years following the date of issuance. The Series B warrants are exercisable immediately upon issuance at an exercise price of $5.00 per ADS and will expire thirty months following the date of issuance.

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H.C. Wainwright & Co. acted as the exclusive placement agent for the offering.

The aggregate gross proceeds to the Company from the private placement was $7.35 million before deducting placement agent fees and other offering expenses. The Company intends to use the net proceeds for general working capital purposes.

The securities described above were offered in a private placement under Section 4(a)(2) of the Securities Act of 1933, as amended (the "Act"), and Regulation D promulgated thereunder and have not been registered under the Act or applicable state securities laws. Accordingly, such securities may not be offered or sold in the United States absent registration with the Securities and Exchange Commission ("SEC") or an applicable exemption from such registration requirements. The securities were offered only to accredited investors. Pursuant to a registration rights agreement with the investors, the Company has agreed to file one or more registration statements with the SEC covering the resale of the ADSs and ADSs issuable upon exercise of warrants.

On November 30, 2022 CNS Pharmaceuticals, Inc. (NASDAQ: CNSP) ("CNS" or the "Company"), a biopharmaceutical company specializing in the development of novel treatments for primary and metastatic cancers in the brain and central nervous system, reported that the pricing of a public offering of an aggregate of (i) 1,889,764 shares of common stock (or pre-funded warrants in lieu thereof), and (ii) warrants (the "Common Warrants") to purchase up to 1,889,764 shares of common stock at a combined public offering price of $3.175 per share (or pre-funded warrant) and associated warrant (Press release, CNS Pharmaceuticals, NOV 30, 2022, View Source [SID1234624622]). The Common Warrants will be immediately exercisable at an exercise price of $3.03 per share and will expire five years following the initial exercise date. The offering is expected to close on or about December 5, 2022, subject to satisfaction of customary closing conditions.

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The Company intends to use the net proceeds of the offering for its ongoing clinical trial, other research and development, and working capital.

H.C. Wainwright & Co. is acting as the exclusive lead placement agent for the offering. Brookline Capital Markets, a division of Arcadia Securities, LLC is acting as the co-placement agent for the offering.

The securities described above are being offered by the Company pursuant to a registration statement on Form S-1 (No. 333-267975) originally filed October 21, 2022 with the Securities and Exchange Commission (SEC) and declared effective by the SEC on November 30, 2022. A final prospectus relating to and describing the terms of the offering will be filed with the SEC and will be available on the SEC’s website at View Source Electronic copies of the final prospectus may be obtained, when available, from H.C. Wainwright & Co., LLC at 430 Park Avenue, 3rd Floor, New York, NY 10022, by phone at (212) 856-5711 or e-mail at [email protected].

The Company also has agreed that certain existing warrants to purchase up to an aggregate of (i) 16,667 shares of common stock at an exercise price of $66.00 and an expiration date of December 28, 2025 and (ii) 210,527 shares of common stock at an exercise price of $24.60 and an expiration date of January 11, 2027 will be amended effective upon the closing of the offering so that the amended warrants will have a reduced exercise price of $3.03 per share and will expire five years following the closing of the offering.

On November 30, 2022 Viracta Therapeutics, Inc. (Nasdaq: VIRX), a precision oncology company focused on the treatment and prevention of virus-associated cancers that impact patients worldwide, reported preliminary dose-ranging data from the first two dose levels of the dose escalation part of the Phase 1b/2 study of Nana-val in patients with EBV+ recurrent/metastatic nasopharyngeal carcinoma (R/M NPC) (Press release, Viracta Therapeutics, NOV 30, 2022, View Source [SID1234624620]). The data are featured in an abstract accepted for a poster presentation at the European Society for Medical Oncology Immuno-Oncology Congress (ESMO-IO), which is taking place both virtually and in-person at the Palexpo Exhibition Centre in Geneva, Switzerland, from December 7 – 9, 2022.

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The Phase 1b/2 trial’s first two dose levels enrolled seven patients with EBV+ R/M NPC, six of whom were evaluable for response as of the abstract’s data cut-off date (September 15, 2022). At the time of enrollment, patients had received a median of two prior systemic therapies. All patients were refractory to their last therapy with bone (6/7), liver (5/7), and lung (3/7) metastases.

Key data reported in the abstract include:

Nana-val was well tolerated with no dose limiting toxicities (DLTs) reported. Most common Grade 1-2 AEs were fatigue, nausea, and increased creatinine (n=3 each).
Two of six evaluable patients achieved stable disease (SD) per RECIST v1.1 criteria.
Plasma EBV DNA titers decreased or remained stable in both patients achieving SD, while rising in patients with progressive disease.
"We initiated this study earlier this year, and this abstract reports the first preliminary data on our all-oral combination regimen in patients with advanced Epstein-Barr virus-positive NPC, where few treatment options are available," said Lisa Rojkjaer, M.D., Chief Medical Officer of Viracta. "Starting with the recommended Phase 2 dose from our Phase 1b/2 study in lymphoma, the combination of nanatinostat and valganciclovir was thus far well-tolerated in the initial dose escalation cohorts, with no DLTs reported. Dose escalation continues as we evaluate optimizing the use of both agents in the solid tumor setting. We look forward to the advancement of this study to determine the recommended Phase 2 dose."

As previously reported, the Phase 1b/2 trial is currently progressing through its third dose escalation cohort, with enrollment in the third dose level completed. Further safety data from the third dose level will be presented in the abstract’s corresponding poster at ESMO (Free ESMO Whitepaper)-IO. Viracta recently amended the trial protocol to include additional dose levels in the Phase 1b dose escalation portion, which is designed to determine the optimal recommended Phase 2 dose (RP2D). The company anticipates initiating the Phase 2 randomized expansion portion of the Phase 1b/2 trial in the second half of 2023.

Additional details related to the abstract and upcoming poster, entitled, A Phase 1b/2 Study of Nanatinostat (Nstat) Plus Valganciclovir (VGCV) in Advanced Epstein-Barr Virus Positive (EBV+) Solid Tumors and with Pembrolizumab (PEM) in Recurrent/Metastatic Nasopharyngeal Carcinoma (R/M NPC), are shown below.

Presentation Number: 156P
Poster Session Date: December 8, 2022
Poster Session Time: 12:30 p.m. CET

The abstract is currently available for viewing on the congress website. A copy of the poster will be available on the "Events and Webcasts" section of the Viracta website following the conclusion of the congress.

About the Phase 1b/2 Trial of Nana-val in EBV+ R/M NPC and Other EBV+ Solid Tumors
This Phase 1b/2 trial (NCT05166577) is an open-label, multinational trial evaluating Nana-val alone and in combination with pembrolizumab. The Phase 1b dose escalation portion is designed to evaluate safety and to determine the recommended Phase 2 dose (RP2D) of Nana-val in patients with EBV+ RM-NPC. In Phase 2, up to sixty patients with EBV+ RM-NPC will be randomized to receive Nana-val at the RP2D with or without pembrolizumab to evaluate safety, overall response rate, and potential pharmacodynamic markers. Additionally, patients with other advanced EBV+ solid tumors will be enrolled to receive Nana-val at the RP2D in a Phase 1b dose expansion cohort.

About Nana-val (Nanatinostat and Valganciclovir)

Nanatinostat is an orally available histone deacetylase (HDAC) inhibitor being developed by Viracta. Nanatinostat is selective for specific isoforms of Class I HDACs, which are key to inducing viral genes that are epigenetically silenced in Epstein-Barr virus (EBV)-associated malignancies. Nanatinostat is currently being investigated in combination with the antiviral agent valganciclovir as an all-oral combination therapy, Nana-val, in various subtypes of EBV-associated malignancies.

About EBV-Associated Cancers

Approximately 90% of the world’s adult population is infected with Epstein-Barr virus (EBV). Infections are commonly asymptomatic or associated with mononucleosis. Following infection, the virus remains latent in a small subset of cells for the duration of the patient’s life. Cells containing latent virus are increasingly susceptible to malignant transformation. Patients who are immunocompromised are at an increased risk of developing EBV+ lymphomas. EBV is estimated to be associated with approximately 2% of the global cancer burden including lymphoma, nasopharyngeal carcinoma and gastric cancer.

On November 30, 2022 TransCode Therapeutics, Inc. (NASDAQ: RNAZ), the RNA oncology company committed to more effectively treating cancer using RNA therapeutics, reported that it has submitted an exploratory Investigational New Drug (eIND) application to the U.S. Food and Drug Administration (FDA) for a planned First-in-Human Phase 0 clinical trial (Press release, TransCode Therapeutics, NOV 30, 2022, View Source [SID1234624619]). The planned clinical trial is to evaluate TransCode’s lead therapeutic candidate, TTX-MC138, in cancer patients with advanced solid tumors. TTX-MC138 is designed to inhibit the pro-metastatic RNA, microRNA-10b, described as the master regulator of metastasis in a number of advanced solid tumors. TransCode believes that TTX-MC138 could be used as a treatment for many of these cancers.

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"We are very excited to take this next step in the development of TTX-MC138 which we hope will bring us closer to introducing this first of its kind treatment for metastatic disease," said TransCode’s Chief Executive Officer and co-founder, Michael Dudley. "We are hopeful that the study conducted under the eIND will demonstrate successful delivery of our lead therapeutic candidate to metastatic lesions in patients with advanced solid tumors. The delivery of oligonucleotide therapeutics to sites other than the liver has remained a significant challenge for decades. Overcoming this challenge would represent an unprecedented step in unlocking therapeutic access to a variety of well documented genetic targets involved in a range of cancers and beyond."

The company believes that TTX-MC138 has the potential to produce regression without recurrence in a range of cancers, including breast, pancreatic, ovarian and colon cancer, glioblastomas and others. In multiple preclinical murine models of triple-negative breast cancer (TNBC), treatment with low-dose chemotherapy and TTX-MC138 eliminated pre-existing local metastases in 100% of treated animals representative of stage II/III metastatic cancer. In a more aggressive model representative of stage IV metastatic cancer, treatment with low-dose chemotherapy and TTX-MC138 resulted in elimination of distant metastases in 65% of animals treated. In a murine model of pancreatic adenocarcinoma, TTX-MC138, administered as monotherapy, resulted in complete responses, manifested as regression without recurrence, in 40% of treated animals. In addition to murine models of cancer, TTX-MC138 was successfully delivered and demonstrated preliminary efficacy in a case study of spontaneous feline mammary carcinoma.

TransCode’s Chief Technology Officer and co-founder, Dr. Zdravka Medarova, said, "Demonstrating the feasibility of delivering TTX-MC138 to malignant lesions in humans could unlock the potential of a wide array of RNA-targeted therapeutics, since the TTX platform permits a modular drug design, centered around the same delivery vehicle but with different payloads in terms of the sequence, design, and mechanism of action of the nucleic acid that is being delivered.

A Phase 0 clinical trial is an exploratory study conducted under an Investigational New Drug application. Exploratory IND studies usually involve very limited human exposure to a therapeutic candidate; their primary purpose is to evaluate the candidate’s safety and mechanism of action. In TransCode’s planned clinical trial, up to 12 patients will be given a single dose of radiolabeled TTX-MC138 followed by noninvasive positron emission tomography-magnetic resonance imaging (PET-MRI). The trial is intended to quantify the amount of radiolabeled TTX-MC138 delivered to metastatic lesions and the pharmacokinetics and biodistribution of the therapeutic candidate in cancer patients. The trial could yield critical data regarding therapeutic dose, timing, and potential safety and could inform later stage clinical trials. This trial is not intended to demonstrate any therapeutic effect.

The eIND application includes data, reports and overview summaries of numerous studies that characterize the pharmacology, pharmacokinetics, and toxicology of the clinical trial version of TTX-MC138 both in vitro and in vivo. Additionally, the application describes the chemistry, manufacturing and control (CMC) production of the drug substance and drug product to be used in the trial. The main purpose of the eIND application is to provide FDA with extensive nonclinical data supporting an acceptable safety profile of a therapeutic candidate to be administered to humans. The FDA is expected to review this application and determine the acceptability of the data before TransCode can begin dosing patients. As with FDA review of Investigational New Drug (IND) applications submitted for Phase 1 clinical trials, an eIND becomes effective 30 days after receipt by the FDA unless FDA, within the 30-day time period, raises concerns or questions about the content of the eIND or clinical trial design.