On October 4, 2023 Viracta Therapeutics, Inc. (Nasdaq: VIRX), a clinical-stage precision oncology company focused on the treatment and prevention of virus-associated cancers that impact patients worldwide, reported that it plans to highlight new preliminary clinical and preclinical data from studies of nanatinostat and valganciclovir (Nana-val), its all-oral investigational therapy targeting Epstein-Barr virus (EBV)-associated cancers, during an R&D Day today, Wednesday, October 4, 2023, at 8:00 a.m. EDT (Press release, Viracta Therapeutics, OCT 4, 2023, View Source [SID1234635652]).

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"We are pleased by the growing clinical data that we believe underscores the therapeutic potential of Nana-val’s innovative ‘Kick and Kill’ approach to target EBV-positive cancer cells and address the adverse survival outcomes seen with most EBV-associated cancers," said Mark Rothera, President and Chief Executive Officer of Viracta. "The clinical responses and favorable safety profile observed in multiple relapsed or refractory EBV-positive lymphoma patient populations continue to be encouraging. New Stage 1 clinical data from patients in the PTCL cohort of the NAVAL-1 trial demonstrated preliminary overall and complete response rates of 40%, which are consistent with our previous Phase 1b/2 study data. Importantly, the combination of response rates and duration of response observed to date in these studies exceeds the current standard of care in this relapsed/refractory patient population. We are on track to complete Stage 2 of the PTCL cohort, targeting to engage with FDA in 2024 on additional requirements for a potential accelerated approval. In addition, we are excited about the emerging signal of dose response in patients with recurrent or metastatic EBV-positive nasopharyngeal carcinoma, now with responses observed at the higher dose levels without dose-limiting toxicities. We look forward to the evaluation of our novel split daily dosing regimen in patients with advanced EBV-positive solid tumors based on compelling preclinical data."

The R&D Day will feature presentations by members of Viracta’s senior management team focusing on its highest priority EBV+ lymphoma indications in the pivotal NAVAL-1 trial, namely, peripheral T-cell lymphoma (PTCL) and diffuse large B-cell lymphoma (DLBCL), as well as its advanced EBV+ solid tumor program in patients with recurrent or metastatic (R/M) EBV+ nasopharyngeal carcinoma (NPC). In addition, the R&D Day will feature presentations by expert key opinion leaders who will discuss the high unmet medical needs of EBV-associated lymphomas.

External speakers will include:

Pierluigi Porcu, M.D., Professor of Medical Oncology, Director of the Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Department of Medical Oncology at Thomas Jefferson University
Robert A. Baiocchi, M.D., Ph.D., Professor of Internal Medicine, Associate Director for Translational and Clinical Science in the Division of Hematology at The Ohio State University
Key R&D Day Topics and Highlights

Initial preliminary data from the pivotal NAVAL-1 clinical trial of Nana-val in patients with relapsed or refractory (R/R) EBV+ lymphoma

As of the data cutoff date of June 30, 2023, initial results from the first five patients with R/R EBV+ PTCL treated with Nana-val showed an overall response rate (ORR) and complete response rate (CRR) of 40%.
The EBV+ PTCL cohort met the efficacy threshold for expansion into Stage 2 of the study, which was based upon having achieved two objective responses within the first five of 10 patients to be enrolled in Stage 1 of the study.
Median duration of response (DoR) has not yet been reached.
Anticipated 2024 milestones:
Completion of enrollment into Stage 2 of the R/R EBV+ PTCL cohort,
Engagement with FDA on additional requirements for accelerated approval,
Presentation of Stage 2 data.
Additional response and durability assessments from the Phase 1b/2 trial (Study 201) of Nana-val in patients with R/R EBV+ lymphoma as of the May 4, 2023 data cutoff date

Median DoR for patients with R/R EBV+ PTCL was 17.3 months with an ORR/CRR of 50%/38% (n=8).
In patients with R/R EBV+ DLBCL, additional response assessments from a formulation pharmacokinetics bridging substudy included two additional responders, one complete response (CR) and one partial response (PR), resulting in an ORR/CRR of 67%/33% (n=9).
Median DoR in the R/R EBV+ DLBCL cohort has not yet been reached, with three patients remaining in response and on continued study treatment with DoRs of 11.1 months (CR), 36.8 months (PR), and 41.9 months (CR).
Additional follow-up further demonstrated that Nana-val was generally well tolerated with manageable, if not reversible, low-grade toxicities; the most commonly observed treatment-emergent adverse events were hematologic or gastrointestinal in nature as well as low-grade creatinine elevations.
New interim clinical data in Phase 1b/2 study of Nana-val in advanced EBV+ solid tumors (Study 301) highlight the opportunity to dose escalate further with an innovative dosing regimen supported by new preclinical data to potentially drive additional responses in this patient population

Enrollment completed through the fifth dose level of the Phase 1b dose escalation portion of the trial without any dose-limiting toxicities reported.
Best responses to date included two PRs (one ongoing for more than seven months) at the higher dose levels plus five stable diseases in 17 patients with R/M EBV+ NPC.
In a preclinical murine EBV+ gastric cancer xenograft model, split daily Nana-val dosing had superior anti-tumor activity than intermittent (four days on/three days off) once-daily dosing, which supports the evaluation of this split daily dosing (SDD) regimen in patients with advanced EBV+ solid tumors.
Anticipated 2024 milestones:
Up to three additional dose levels are planned with Nana-val on an SDD schedule to select a recommended Phase 2 dose,
Initiation of the clinical trial’s randomized Phase 2 expansion cohort designed to evaluate Nana-val at the recommended Phase 2 Dose (RP2D) with or without pembrolizumab in patients with R/M EBV+ NPC,
Initiation of the clinical trial’s exploratory Phase 1b expansion cohort designed to evaluate Nana-val at the RP2D in patients with other advanced EBV+ solid tumors, including gastric carcinoma, leiomyosarcoma, and lymphoepithelioma.
R&D Day Webcast Information
A live video webcast of the presentation will be available here and on the Investors section of the Viracta website under "Events and Webcasts". A replay of the presentation will be available approximately one hour after the presentation and will be archived and available for at least 30 days following the event at the same location.

About NAVAL-1
NAVAL-1 (NCT05011058) is a global, multicenter, clinical trial of Nana-val in patients with relapsed or refractory (R/R) Epstein-Barr virus-positive (EBV+) lymphoma. This trial employs a Simon two-stage design where, in Stage 1, participants are enrolled into one of three prioritized indication cohorts based on EBV+ lymphoma subtype. If a pre-specified antitumor activity threshold is reached within a lymphoma subtype in Stage 1 (n=10), then additional patients will be enrolled in Stage 2 for a total of 21 patients. EBV+ lymphoma subtypes demonstrating promising antitumor activity in Stage 2 may be further expanded following discussion with regulators to potentially support registration.

About the Phase 1b/2 Study of Nana-val in R/M EBV+ NPC and Other EBV+ Solid Tumors
This Phase 1b/2 trial (NCT05166577) is an open-label, multinational clinical trial evaluating Nana-val alone and in combination with pembrolizumab. The Phase 1b dose escalation part is designed to evaluate safety and to determine the recommended Phase 2 dose (RP2D) of Nana-val in patients with recurrent or metastatic (R/M) Epstein-Barr virus-positive (EBV+) nasopharyngeal carcinoma (NPC). In Phase 2, up to 60 patients with R/M EBV+ NPC will be randomized to receive Nana-val at the RP2D with or without pembrolizumab to further evaluate antitumor activity, safety and tolerability, pharmacokinetics, and potential pharmacodynamic biomarkers. 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. Ongoing trials include a pivotal, global, multicenter, open-label Phase 2 basket trial in multiple subtypes of relapsed or refractory (R/R) EBV+ lymphoma (NAVAL-1) as well as a multinational Phase 1b/2 clinical trial in patients with recurrent or metastatic (R/M) EBV+ NPC and other EBV+ solid tumors.

About EBV-Associated Cancers
Approximately 90% of the world’s adult population is infected with 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-positive (EBV+) lymphomas. EBV is estimated to be associated with approximately 2% of the global cancer burden including lymphoma, nasopharyngeal carcinoma (NPC), and gastric cancer.

On October 4, 2023 Veracyte, Inc. (Nasdaq: VCYT) reported that new data from a large, randomized phase 3 trial reinforce the value of the Decipher Prostate Genomic Classifier in helping physicians make more informed treatment decisions for their patients with prostate cancer (Press release, Veracyte, OCT 4, 2023, View Source [SID1234635651]). The findings, presented at the 2023 American Society for Radiation Oncology (ASTRO) Annual Meeting, suggest that the Decipher Prostate test can categorize more accurately risk of patients with clinically high-risk disease to help inform appropriate treatment.

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Data from a second study presented at ASTRO 2023 reveal there is minimal to moderate risk-score correlation between the gene expression signatures of three commercially available genomic classifiers, including the Decipher Prostate test. The study authors suggest that, given the lack of correlation seen in the cross-comparison, the level of evidence supporting each genomic test, per nationally recognized consensus guidelines, should drive utilization.

"The findings presented at ASTRO 2023 add to the large body of evidence, which now includes 12 phase 3 randomized trials, demonstrating the Decipher Prostate classifier’s performance as a tool to help guide therapeutic decisions in prostate cancer," said Elai Davicioni, Ph.D., Veracyte’s medical director for Urology. "Furthermore, they reinforce that the substantial level of evidence supporting the Decipher Prostate test can help guide its selection and utilization for patients with prostate cancer."

The first study assessed the prognostic performance of the Decipher Prostate test among clinically high-risk patients with localized prostate cancer from the phase 3, randomized NRG RTOG 0521 clinical trial, who received radiation and two years of androgen deprivation therapy (ADT) with or without docetaxel chemotherapy. Researchers generated Decipher Prostate test scores using biopsy samples from 183 patients, who were followed for a median of 9.9 years.

Results show that only the Decipher Prostate risk score was independently associated with metastasis-free survival (MFS; HR 1.12, 95% CI) and distant metastasis (DM; sHR 1.22, 95% CI), compared to standard risk factors including Gleason score, T-stage and prostate-specific antigen (PSA) level. Additionally, patients with higher-risk Decipher Prostate genomic scores had worse DM (sHR 2.82, 95% CI) compared to those with lower-risk scores. Cumulative DM at 10 years was 27% for those with higher-risk Decipher test scores vs. 9% for those with lower-risk Decipher test scores (95% CI).

"This study reinforces the ability of the Decipher Prostate classifier to improve risk stratification in high-risk prostate cancer, and thereby support more informed, personalized treatment decisions for these patients," said Phuoc T. Tran, M.D., Ph.D., professor and vice chair for research of Radiation Oncology at the University of Maryland School of Medicine, and co-senior investigator for the study.

In the second study, researchers sought to determine whether risk-score correlation between three commercially available gene expression signatures, including the Decipher Prostate Genomic Classifier, which has the highest level of evidence according to clinical practice guidelines, is strong enough to use the three tests interchangeably. Signature scores for the tests were compared in biopsy samples from over 50,000 patients with localized prostate cancer. The results show that there is a minimal to moderate level of correlation between the three gene expression signatures.

"The poor correlation we observed between the three risk scores suggests that these tests may not be used interchangeably, and clinicians should base utilization on the levels of evidence supporting them," said Daniel Spratt, M.D., Vincent K. Smith chair of Radiation Oncology at University Hospitals Seidman Cancer Center and professor and chair of the Department of Radiation Oncology at Case Western Reserve University School of Medicine, and lead investigator for the study.

On October 4, 2023 Sigyn Therapeutics, Inc. ("Sigyn" or the "Company") (OTCQB: SIGY), a development-stage medical technology company, reported the submission of a Patent Cooperation Treaty (PCT) application entitled: "SYSTEM AND METHODS TO ENHANCE CHEMOTHERAPY DELIVERY AND REDUCE TOXICITY (Press release, Sigyn Therapeutics, OCT 4, 2023, View Source [SID1234635649])."

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The PCT submission is associated with medical technologies being advanced by Sigyn Therapeutics to enhance the clinical benefit of chemotherapeutic drugs administered to cancer patients. Among therapeutic technologies being developed by the Company are ChemoPrepTM and ChemoPureTM. Chemotherapy is the most commonly administered drug to treat cancer, the second leading cause of death in the United States. Despite utility across a broad-spectrum of cancers, there remains a critical need to optimize chemotherapy delivery as less than 5% of administered doses reach their tumor-site target.

ChemoPrepTM is being advanced to extract circulating molecules that restrict the tumor-site delivery of chemotherapy and induce an unresponsiveness to therapy (chemoresistance) associated with 90% of metastatic cancer deaths. The clinical intent of ChemoPrepTM is to safely increase the tumor-site saturation of chemotherapeutic agents with reduced doses. Achievement of this objective will likely improve treatment outcomes yet reduce treatment toxicity and long-term health consequences associated with chemotherapy administration. Beyond the potential to increase survival and enhance patient quality of life, reduced dosing of chemotherapeutic agents may alleviate ongoing supply chain issues associated with nationwide shortages of chemotherapy.

Post infusion of chemotherapy, Sigyn Therapeutics designed ChemoPureTM to extract off-target drug agents from the bloodstream as a means to further reduce patient toxicity.

The Patent Cooperation Treaty (PCT) is an international treaty with more than 150 Contracting States. A PCT submission makes it possible to seek patent protection for an invention simultaneously in a large number of countries by filing a single "international" patent application instead of filing multiple national or regional patent applications. However, the granting of patents remains under the control of the national or regional patent offices. Sigyn Therapeutics previously disclosed that a related provisional patent application was filed with the United States Patent and Trademark Office ("USPTO").

On October 4, 2023 Shorla Oncology (‘Shorla’), a U.S.-Ireland specialty pharmaceutical company, reported that it has raised $35 million in Series B funding, led by Kurma Partners’ Growth Opportunities Fund, with participation from existing investors Seroba Life Sciences and Irish, U.S. and Canadian based family offices and Enterprise Ireland (Press release, Shorla Oncology, OCT 4, 2023, View Source;utm_medium=rss&utm_campaign=press-release-shorla-oncology-secures-35m-series-b-funding-round-to-advance-its-oncology-product-portfolio [SID1234635648]). The funding will enable Shorla to accelerate the growth of its oncology portfolio by advancing its pipeline, bringing therapies to market that will address drug shortages, and improving the preparation and application of oncology medication(1).

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"We are thrilled to announce the successful conclusion of our Series B funding round," stated Sharon Cunningham, chief executive officer of Shorla Oncology. "The investment will underpin the advancement and commercialization of our oncology drugs ensuring we continue to deliver on our mission of bringing promising treatments to patients around the globe."

Shorla specializes in the development of oncology treatments, with a focus on orphan and pediatric cancers. Backed by a dedicated team of scientists and clinicians, the company is advancing a differentiated portfolio of oncology treatments aimed at addressing significant gaps in patient care. Shorla recently announced the FDA approval and market launch of Nelarabine Injection, marking its first approval in the US. Shorla aims to continuously bring further products to market with a significant and growing portfolio of late-stage assets. These products are improving efficiencies by providing more convenient formulations to clinicians and enabling easier application for patients(2).

"Shorla’s recent FDA approval is a testament to its capabilities for bringing differentiated formulations of life-changing medications to the market," commented Daniel Parera, M.D., Partner, Kurma Partners. "We are excited to support Shorla’s growth as an integrated Specialty Pharma company to address shortcomings in patient care and improve outcomes. In particular, the team has shown impressive agility in identifying unmet needs and in operational execution. This matches very well with our focus and expertise as a Growth fund to support the scale-up of emerging champions of the European Healthcare and Life Science ecosystem."

On October 4, 2023 Revolution Medicines, Inc. (Nasdaq: RVMD), a clinical-stage oncology company developing targeted therapies for RAS-addicted cancers, reported the company will present new clinical data for two of its RAS(ON) Inhibitors and other investigational compounds at upcoming oncology conferences, the 2023 AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) ("Triple Meeting") in Boston, Massachusetts, to be held October 11-15, and the 2023 European Society for Medical Oncology Congress (ESMO) (Free ESMO Whitepaper) in Madrid, Spain, to be held October 20-24 (Press release, Revolution Medicines, OCT 4, 2023, View Source [SID1234635647]).

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At the Triple Meeting, the company will present the first report of clinical activity for RMC-6291, its RASG12C(ON) Inhibitor and additional preliminary safety and pharmacokinetic profiles for RMC-6236, its RASMULTI(ON) Inhibitor. At ESMO (Free ESMO Whitepaper), the company will present additional preliminary antitumor activity data for RMC-6236 in patients with non-small cell lung cancer (NSCLC) or pancreatic ductal adenocarcinoma (PDAC) carrying common KRASG12X mutations. The abstract related to this presentation, which will go live on the ESMO (Free ESMO Whitepaper) website at 0:05 CEST on October 16, 2023 (6:05 p.m. ET, October 15), will include data from an April 24, 2023 data extraction, while the Proffered Paper presentation itself will include more recent data from an October data extraction.

Shortly following the company’s ESMO (Free ESMO Whitepaper) data presentation, the company will host an investor webcast to review the clinical data presentations on RMC-6236 and RMC-6291, related clinical development vision, and the company’s overall pipeline and strategy.

Details of the presentations referenced above, as well as other presentations by the company at these conferences, are listed below:

Triple Meeting Oral Presentations:

Title: Targeting RAS-addicted cancers with investigational RAS(ON) inhibitors
Presenter: W. Clay Gustafson, M.D.
Session: Plenary Session 3: KRAS
Date/Time: 8:00 – 9:40 a.m. ET on October 13, 2023

Title: Preliminary safety and pharmacokinetic profiles of RMC-6236, a first-in-class,
RAS-selective, tri-complex RASMULTI(ON) inhibitor in patients with KRAS mutant
solid tumors on the Phase 1 trial RMC-6236-001
Presenter: Alexander I. Spira
Abstract Number: B032*
Session: Plenary Session 4: New Drugs on the Horizon
Date/Time: 9:40 – 11:45 a.m. ET on October 13, 2023
*Also included in Poster Session B on October 13, from 12:30 to 4:00 p.m. ET.

Title: Preliminary safety and anti-tumor activity of RMC-6291, a first-in-class, tri-complex
KRASG12C (ON) inhibitor, in patients with or without prior KRASG12C (OFF) inhibitor
treatment
Presenter: Pasi A. Jänne
Abstract Number: LB_B01*
Session: Spotlight on Proffered Papers 2
Date/Time: 11:50 a.m. – 12:20 p.m. ET on October 13, 2023
*Also included in Poster Session B on October 13, from 12:30 to 4:00 p.m. ET.

Triple Meeting Poster Presentations:

Title: Selective inhibition of the active state of KRASG12V with the non-covalent, tri-complex
Inhibitor RM-048
Presenter: Bianca J. Lee, Ph.D.
Abstract Number: B137
Session: Poster Session B
Date/Time: 12:30 – 4:00 p.m. ET on October 13, 2023

Title: First-in-human phase 1/1b trial of the first-in-class bi-steric mTORC1-selective inhibitor RMC-5552 in patients with advanced solid tumors
Presenter: Alison M. Schram, M.D.
Abstract Number: C020
Session: Poster Session C
Date/Time: 12:30 – 4:00 p.m. ET on October 14, 2023

Additional information on the Triple Meeting is available through the conference website at: View Source

ESMO Oral Presentation:

Title: Preliminary clinical activity of RMC-6236, a first-in-class, RAS-selective, tri-complex RASMULTI(ON) inhibitor in patients with KRAS mutant pancreatic ductal adenocarcinoma (PDAC) and non-small cell lung cancer (NSCLC)
Presenter: Kathryn C. Arbour, M.D.
Abstract Number: 6520
Session: Proffered Paper Session – Developmental Therapeutics
Date/Time: 08:30 – 10:00 a.m. CEST (2:30 – 4:00 a.m. ET) on October 22, 2023

Additional information on the ESMO (Free ESMO Whitepaper) Congress is available through the conference website at: View Source

Investor Webcast
Revolution Medicines will host an investor webcast on Sunday, October 22, 2023, at 12:30 p.m. ET. The presentation will review the clinical data presentations on RMC-6236 and RMC-6291 highlighted above, related clinical development vision, and the company’s overall pipeline and strategy. To participate in the live webcast, participants may register in advance here: View Source A live webcast of the call will also be available on the Investors section of Revolution Medicines’ website at View Source Following the live webcast, a replay will be available on the company’s website for at least 14 days.