On April 17, 2023 Veracyte, Inc. (Nasdaq: VCYT) reported that new data published in European Urology Oncology suggest the Decipher Prostate Genomic Classifier could help identify prostate cancer patients who have micrometastatic disease (difficult-to-detect tumor cells that extend beyond the prostate) and who may therefore benefit from systemic treatment intensification (Press release, Veracyte, APR 17, 2023, View Source [SID1234630178]). The data show that, in men with high-risk and very high-risk disease, Decipher Prostate scores are highly correlated with upstaging predictions made by a clinical algorithm shown to predict prostate-specific membrane antigen (PSMA) positron emission tomography (PET) positivity.

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"Prostate cancer patients with clinically high-risk and very high-risk disease are prone to treatment failure due to micrometastatic disease that was not detected at the time of initial presentation, so it is imperative that we have tools to accurately identify these patients and intensify their treatment accordingly," said Amar U. Kishan, vice chair of Clinical and Translational Research and chief of the Genitourinary Oncology Service, UCLA Jonsson Comprehensive Cancer Center, and an investigator for the study. "Our findings suggest that a high Decipher Prostate score is highly correlated with the risk of having disease outside the prostate identified on advanced molecular imaging. These patients are likely to benefit from upfront systemic treatment intensification. Ongoing clinical trials are designed to prove this."

The 22-gene Decipher Prostate Genomic Classifier provides a score ranging from 0 to 1, categorized as low (<0.45), intermediate (0.45-0.60) and high risk (>0.60) of metastasis. It is the most validated prognostic biomarker for identifying metastatic disease risk among individuals with prostate cancer to help determine who may benefit from treatment intensification. It is currently being evaluated for its role as a predictive biomarker to guide systemic therapy intensification or deintensification in two large, Phase 3 clinical trials (NRG-GU009, NRG-GU010).

In the current study, researchers sought to quantify the association between the risk of upstaging on PSMA PET using a validated clinical algorithm for PSMA PET positivity developed by researchers at UCLA, and the Decipher Prostate score. Using data from 4,625 prostate cancer patients who met the criteria for NCCN high-risk or very high-risk disease or met the high-risk criteria for the STAMPEDE clinical trial, they calculated the probability of upstaging on PSMA PET using the established, validated clinical nomogram, and correlated this risk and individual patients’ Decipher Prostate scores.

The researchers found that there was a significant correlation between patients’ Decipher Prostate scores and the risk of upstaging on PSMA PET, and that high Decipher scores were especially enriched in patients at the highest risk of harboring disease outside their prostate. Accordingly, these patients would be more likely to benefit from systemic treatment intensification as compared to local therapy.

"These findings reinforce the evidence supporting the Decipher Prostate test’s ability to help inform treatment decision-making at initial prostate cancer diagnosis. We look forward to long-term data from ongoing, prospective trials such as NRG-GU009 to help verify the prognostic and predictive power of the Decipher Prostate test to guide treatment intensification or deintensification in patients with high-risk prostate cancer," said Elai Davicioni, Ph.D., Veracyte’s medical director for Urology.

On April 17, 2023 Tempest Therapeutics, Inc. (Nasdaq: TPST), a clinical-stage oncology company developing first-in-class1 therapeutics that combine both targeted and immune-mediated mechanisms, reported that new data from its TPST-1120 and TREX1 programs were highlighted in two poster presentations at the 2023 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting taking place April 14-19, 2023 in Orlando, FL (Press release, Tempest Therapeutics, APR 17, 2023, View Source [SID1234630177]).

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The presentation for TPST-1120, a clinical-stage oral selective PPAR⍺ antagonist, highlighted new translational biomarker findings from the completed monotherapy and nivolumab combination therapy dose escalation Phase 1 trial showing on-target changes in gene signatures in the peripheral blood that were dependent upon drug exposure levels. In addition, distinct on-target changes in both lipid profile and NF-κB pathway regulated immune response gene signatures were observed in patients who achieved a RECIST response, compared with non-responders, following treatment with TPST-1120 and nivolumab.

The presentation for Tempest’s preclinical TREX1 inhibitor program, designed for tumor-selective activation of the STING pathway, is the first public demonstration of human TREX1 enzyme—TREX1 inhibitor X-ray co-crystal structures, which has facilitated the development of potent and specific TREX1 inhibitors with drug-like properties. Lead series molecules resulting from this activity demonstrated therapeutic benefit in tumor-bearing preclinical models.

"We are very excited to report these significant advances in the TPST-1120 and TREX1 programs," said Tom Dubensky, Ph.D., president of Tempest. "We look forward to the further clinical development of TPST-1120, potentially in multiple oncology indications, and are working to develop a TREX1 inhibitor to begin human clinical trials with this differentiated approach designed to selectively activate the STING pathway broadly in advanced metastatic disease."

About TPST-1120

TPST-1120 is an oral, small molecule, selective PPAR⍺ antagonist. Tempest’s preclinical data suggest that TPST-1120 can kill tumor cells directly and target suppressive immune pathways in the tumor microenvironment. Both types of targeted cells can be dependent on fatty acid metabolism, which is regulated by the PPAR⍺ transcription factor. In extensive non-clinical studies, TPST-1120 as a monotherapy or in combination with other anti-cancer drugs resulted in significant reductions in tumor growth and stimulation of durable anti-tumor immunity. In a Phase 1 clinical trial in patients with heavily-pretreated advanced solid tumors, TPST-1120 as monotherapy and in combination with the PD-1 inhibitor, nivolumab, demonstrated tumor reduction (including according to RECIST criteria), as well as biomarker modulation. TPST-1120 was well-tolerated both as a monotherapy and in combination with nivolumab. In addition, enrollment has completed in a Phase 1b/2 clinical trail conducted with F. Hoffman La-Roche, evaluating TPST-1120 + atezolizumab + bevacizumab in a randomized head-to-head comparison to atezolizumab + bevacizumab in the first line treatment of patients with unresectable or metastatic HCC. Initial results from this randomized study are expected in the first half of 2023.

About TREX1

TREX1 is a cytoplasmic DNA exonuclease that is upregulated in tumor cells in response to tumor growth, genomic instability and therapeutic intervention. TREX1 is both a negative regulator of the cGAS/STING signaling pathway and a DNA repair enzyme. Orally available TREX1 inhibitors are expected to both selectively inhibit tumor growth and induce tumor-specific immunity broadly against advanced metastatic disease. Tempest has shown proof of concept in animal models with this approach and is currently advancing a small molecule series through lead optimization.

On April 17, 2023 Sysmex Inostics Inc., a subsidiary of Japan’s Sysmex Corporation and Baltimore-based biotechnology firm and CLIA-certified lab, reported that it is exhibiting at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023 in Orlando, FL from April 16, 2023, through April 19, 2023 (Press release, Sysmex Inostics, APR 17, 2023, View Source [SID1234630176]). The company is exhibiting at "Booth 1325" to meet with the over 20,000 global cancer research professionals in attendance.
While at AACR (Free AACR Whitepaper), Sysmex Inostics will take applications for its Cancer Research Excellence Program (CREP) announced in February. Winning cancer researchers receive free testing services of the company’s Plasma-Safe-SeqS technology, breast cancer or RAS-RAF signaling pathway panels. The program is open to U.S. solid tumor researchers at academic, medical, non-profit or government organizations; acceptance of applications ends on April 30, 2023.

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"At Sysmex Inostics we value every person, decision, and molecule within the therapeutic research journey including at the academic bench," said Shinichi Sato, President, and CEO of Sysmex Inostics. "Our CREP extends our reach into the medical research market increasing the adoption of our sensitive liquid biopsy technology, Plasma-Safe-SeqS, while also advancing critical early scientific discoveries."

Showcases New BioPharma Market Offering

On April 13th the company announced a strategic partnership with Genomic Testing Cooperative (GTC), a molecular testing company in Irvine, CA, for Sysmex Inostics to commercialize GTC’s DNA and RNA next generation sequencing (NGS) services to BioPharma customers. The partnership synergizes GTC’s proprietary testing, genomic databases, artificial intelligence (AI) technology with Sysmex Inostics’ global commercial capabilities in BioPharma therapeutic development and highly sensitive Plasma-Safe-SeqS technology.

BioPharma researchers and patients now have access to the testing they need at every stage of the clinical trial process from Sysmex Inostics. GTC’s suite of genomic assays – Solid Tumor Profile Plus, Liquid Trace Solid Tumor Profile, Liquid Trace Hematology Profile, and Hematology Profile Plus – allows BioPharma researchers tissue and liquid biopsy solid tumors and hematology assay services while discovering new molecules. While Sysmex Inostics’ CLIA-validated Plasma-Safe-SeqS ultra-sensitive liquid biopsy technology allows BioPharma to expedite clinical trial patient enrollment knowing patients are being monitored with one of the most sensitive liquid biopsy tests on the market.

"At Sysmex Inostics we understand how drugs are developed and we know not one test fits all stages of the process. It was imperative to offer our BioPharma partners broader panels for their discovery work. Our new partnership with GTC for pan-cancer testing services and existing collaboration with QIAGEN, for CDx development and regulatory submission, gives us the ability to support the entire therapeutic development journey," said Sato.

GTC has established a network of cooperative testing facilities that enable testing in clinical settings and in support of BioPharma research products with available Medicare reimbursement. The companies will work jointly on improvements and new indications of the tests for use by researchers.

On April 17, 2023 Sporos BioDiscovery, Inc. (a wholly owned affiliate of Sporos Bioventures, "Sporos" or the "Company"), a precision oncology company developing a diversified pipeline of small molecule therapeutic candidates, reported preclinical data for its lead candidate, SPR1-0117, a next-generation TEAD inhibitor at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023 in Orlando, FL (Press release, Sporos Bioventures, APR 17, 2023, View Source [SID1234630175]).

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SPR1-0117 targets cancers driven by mutations in the Hippo pathway, a key regulator of cell proliferation and oncogenesis not yet extensively targeted in precision oncology. The YAP1/TAZ co-activators and the TEAD family of transcription factors, which consists of four paralogs (TEAD1-4), execute the pro-cancerous effects of the Hippo pathway through transcription of pro-proliferative and anti-apoptotic genes. Hippo pathway activation has also emerged as a key mechanism of resistance to inhibitors of the MAPK pathway, making TEAD inhibitors a prime candidate for combination therapy with therapeutics targeting the MAPK pathway.

Sporos BioDiscovery’s bioinformatic analyses identified that selective inhibition of both TEAD1 and TEAD4 drives improved biological impact as compared to TEAD1 inhibitors alone, while inhibition of TEAD2 and TEAD3 were observed as undesirable due to the potential for paradoxical adverse stimulation of cell proliferation and kidney toxicity, respectively.

"We are excited to share this new data demonstrating the deep and broad biological activity of SPR1-0117 both in vitro and in vivo, not only in benchmark models of cancers driven by Hippo-pathway mutations but in a number of cell lines beyond that of mesothelioma and NF2 mutations, including in cell lines showing only a nuclear YAP/TAZ hyperactivity. We believe this broad activity is driven by SPR1-0117’s isoform selectivity profile which inhibits both TEAD1 / TEAD4. We believe this profile may unlock the potential of SPR1-0117 as a monotherapy in a wide array of tumors with Hippo driver mutations compared to inhibitors binding primarily TEAD1," said Stephen Rubino, Ph.D., Chief Executive Officer of Sporos Bioventures.

Dr. Rubino continued "We also see greater depth of biological response in benchmark models, with close to 80% frank regression in large, established tumors, a feat unaccomplished by other TEAD inhibitors to date. Overall, we believe SPR1-0117’s TEAD1 / TEAD4 isoform selectivity profile has been optimized as a potential best-in-class TEAD inhibitor for both monotherapy and in combination with MAPK and RTK inhibitors. We are on track to initiate IND-enabling studies for our TEAD inhibitor program this quarter and look forward to advancing our lead candidate into the clinic in 2024."

Data reported in the poster presentation from AACR (Free AACR Whitepaper) demonstrated SPR1-0117 has showed strong monotherapy activity across multiple in vitro models, including several non-mesothelioma cell lines. In addition, SPR1-0117 shows low nM potency and strong single-agent activity against TEAD-dependent benchmark in vivo models, including H226 NF2-null mesothelioma, as well as in vivo efficacy beyond mesothelioma in SCC25, an oral squamous cell carcinoma. SPR1-0117 has also demonstrated a promising ADME and safety profile in preclinical models and was shown to be well tolerated, including no significant findings of kidney toxicity, in a seven-day repeat dosing study in rats at greater than 10-times the drug exposure required for efficacy in mice.

The published poster is now available in the News & Events section of the Sporos Bioventures website.

On April 17, 2023 Sonnet BioTherapeutics Holdings, Inc. (NASDAQ:SONN), a clinical-stage company developing targeted immunotherapeutic drugs, reported that the company will host a webcast to share data from its SB101 clinical study with SON-1010 in oncology patients (NCT05352750) on Tuesday, April 18, 2023 at 5:00 pm ET (Press release, Sonnet BioTherapeutics, APR 17, 2023, View Source [SID1234630173]).

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Webcast presenters will include:

Richard Kenney, M.D., Chief Medical Officer
Pankaj Mohan, Ph.D., Sonnet Founder and Chief Executive Office

The webcast at 5:00 pm ET, with an accompanying presentation, will be accessible under News & Events, IR Calendar in the Investors section of the company’s website. The archived audio webcast will be available on Sonnet’s website following the call.

To participate in the webcast, please see the following details:

Webcast Link: View Source;tp_key=f6d5c78778
Toll Free: 1-877-869-3847
International: 201-689-8261
Conference ID: 13737737
AACR Poster Presentation Details:

Title: Clinical development of a novel form of interleukin-12 with extended pharmacokinetics
Session Title: Phase I and First-in-Human Clinical Trials in Progress
Presentation Type: Poster
Session Date and Time: Tuesday April 18, 2023, 1:30 pm – 5:00 pm ET
Abstract Number: CT245
Location: Poster Section 46