On September 8, 2021 Strata Oncology, Inc., a precision oncology company advancing molecular indications for cancer therapies, reported that results from validation studies demonstrating the reliable performance of the StrataNGS test were published in The Journal of Molecular Diagnostics (Press release, Strata Oncology, SEP 8, 2021, View Source [SID1234587442]). StrataNGS is a 429-gene, multiplex PCR-based comprehensive genomic profiling (CGP) test performed on co-isolated DNA and RNA from formalin-fixed paraffin-embedded (FFPE) tissue tumor specimens with >2mm2 tumor surface area.

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Through a unique assay configuration and novel bioinformatics pipeline optimized for multiplex PCR-based sequencing, StrataNGS demonstrated high sensitivity and specificity for detecting single nucleotide variants, insertions/deletions, gene fusions, copy number alterations, microsatellite instability and tumor mutation burden. Designed to provide comprehensive assessment of clinically actionable biomarkers from minute FFPE solid tumor tissue samples, StrataNGS substantially increases patient access to tissue-based CGP. A recent study of >30,000 real-world tumor tissue samples received for CGP found that only 41.6% of samples met minimum tissue requirements (>25mm2 tumor surface area) for several leading hybrid capture-based CGP tests.

"StrataNGS demonstrated the sensitivity and specificity required for routine clinical practice while reporting all CGP variant classes from minute FFPE tissue samples," said Scott Tomlins, M.D., Ph.D., co-founder and Chief Medical Officer, Strata Oncology. "Conventional tissue-based CGP and liquid biopsy tests often fail to meet either the sensitivity or success rate needed to deliver reliable results for each patient. StrataNGS nearly eliminates the insufficient tissue problem, while delivering the sensitivity required to confidently rule-in or out a treatment. This approach directly translates into treatment insights for more patients."

About StrataNGS
StrataNGS is a comprehensive genomic profiling (CGP) test that features the lowest tumor tissue requirements in the industry (≥2mm2 surface area). The 429-gene assay is performed on co-isolated RNA and DNA. Single-/multi-nucleotide variants (SNVs), short insertions and deletions (indels), copy number alterations (CNAs; amplifications and deep deletions), microsatellite instability (MSI) status, gene fusions, and tumor mutation burden (TMB) are assessed simultaneously.

On September 08, 2021 Selecta Biosciences, Inc., a biotechnology company leveraging its clinically validated ImmTOR platform to develop tolerogenic therapies that selectively mitigate unwanted immune responses, and Cyrus Biotechnology, Inc. a leading protein design company, reported a protein engineering collaboration combining Selecta’s ImmTOR platform with Cyrus’ ability to radically redesign protein therapeutics (Press release, Selecta Biosciences, SEP 8, 2021, View Source [SID1234587493]). The lead program in the collaboration is a proprietary interleukin-2 (IL-2) protein agonist designed to selectively promote expansion of regulatory T cells (Treg) for the treatment of patients with autoimmune diseases and other deleterious immune conditions.

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Novel IL-2 approaches and technologies are driving innovation in the therapeutic development space. The IL-2 pathway influences critical aspects of both immune stimulation and immune regulation, through the development and expansion of regulatory T cells (Treg). These Treg cells are a specialized subpopulation of T cells involved in suppressing certain immune responses and maintaining the body’s self-tolerance. Reductions in the number of Treg cells have been shown to drive a spectrum of autoimmune diseases and conversely, increasing Treg expansion may have clinical utility in reducing inflammation and improving disease outcomes. Early preclinical data investigating the effects of ImmTOR in combination with a Treg-selective IL-2 mutant protein (IL-2 "mutein") demonstrate substantial synergistic activity in increasing the percentage and durability of Treg expansion in the spleen (Figure below). This supports the potential of ImmTOR in combination with IL-2 proteins to restore immunotolerance to autoantigens and forms the basis for this partnership. Although IL-2 has been an attractive target for autoimmune indications, overcoming its immunostimulatory activities, short half-life and anti-IL-2 antibody formation has been challenging. Building on recent advancements in the field, our strong preliminary data suggest that ImmTOR in combination with Cyrus’ novel IL-2 protein agonist has the potential to unlock the value of this target and drive the development of a next generation, best-in-class asset.

A figure accompanying this announcement is available at View Source

"We are excited to collaborate with Cyrus, and we see this strategic protein engineering partnership as an important step in advancing our ImmTOR platform for the treatment of autoimmune diseases," said Carsten Brunn, Ph.D., President and Chief Executive Officer of Selecta. "We are encouraged by the preclinical data generated to date and the growing literature that supports the potential of IL-2 therapeutics in treating immunological diseases."

Dr. Brunn added, "We look forward to leveraging Cyrus’ ability to both reengineer immune epitopes and rationally design novel proteins using non-traditional starting sequences, including non-human, non-natural and ancestral versions. For our first program, this combination will allow us to potentially mitigate unwanted immune responses by reducing the inherent immunogenicity of the protein while also promoting immune tolerance. We are fortunate to have this opportunity to optimize and advance our portfolio through the design and generation of innovative protein therapeutics. Beyond leading a paradigm shift in the way biologics are made, ultimately this collaboration has the potential to unlock new treatment options and improve the lives of patients who suffer from serious and debilitating diseases."

Lucas Nivon, Ph.D., Chief Executive Officer of Cyrus, commented, "We welcome Selecta as a deeply experienced partner. This collaboration is in perfect alignment with our protein design expertise and represents an important endorsement of our platform, which has the potential to further enhance the potency of ImmTOR’s tolerizing power. With our current partners, we have demonstrated our ability to redesign existing protein biologics or build them from the ground-up — expanding the potential for therapeutics and intellectual property. We look forward to executing on our shared vision."

Under the terms of the collaboration, Selecta has provided an upfront payment, and Cyrus is eligible to earn discovery, development and sales based milestones. Novel engineered protein therapeutic candidates from the partnership will be used to expand Selecta’s proprietary pipeline and further bolster Selecta’s clinically validated ImmTOR platform.

On September 8, 2021 AstraZeneca PLC ("AstraZeneca") (LSE/STO/Nasdaq:AZN) reported that they have initiated SANOVO, a China Phase III study of ORPATHYS (savolitinib), an oral, potent, and highly selective MET tyrosine kinase inhibitor ("TKI"), in combination with AstraZeneca’s third-generation, irreversible epidermal growth factor receptor ("EGFR") TKI, TAGRISSO (osimertinib) as a first-line treatment in certain non-small cell lung cancer ("NSCLC") patients whose tumors harbor EGFR mutation and overexpress MET (Press release, Hutchison China MediTech, SEP 8, 2021, View Source [SID1234590537]). The first patient was dosed on September 7, 2021.

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The Phase III trial is a blinded, randomized, controlled study in previously untreated patients with locally advanced or metastatic NSCLC with activating EGFR mutations and MET overexpression. The study will evaluate the efficacy and safety of TAGRISSO in combination with ORPATHYS comparing to TAGRISSO alone, a standard-of-care treatment option for these patients. The primary endpoint of the study is median progression free survival ("PFS") as assessed by investigators. Other endpoints include median PFS assessed by an independent review committee, median overall survival ("OS"), objective response rate ("ORR"), duration of response ("DoR"), disease control rate ("DCR"), time to response (TTR), and safety. Additional details may be found at clinicaltrials.gov, using identifier NCT05009836.

About NSCLC, EGFR and MET Aberrations
Lung cancer is the leading cause of cancer death among men and women, accounting for about one-fifth of all cancer deaths.[1] More than a third of the world’s lung cancer patients are in China.[2] Lung cancer is broadly split into NSCLC and small cell lung cancer, with 80-85% classified as NSCLC.[3] The majority of NSCLC patients are diagnosed with advanced disease while approximately 25-30% present with resectable disease at diagnosis.[4],[5] For patients with resectable tumors, the majority of patients eventually develop recurrence despite complete tumor resection and adjuvant chemotherapy.[6]

Approximately 10-25% of NSCLC patients in the US and Europe, and 30-40% of patients in Asia have EGFR-mutated NSCLC.[7],[8],[9] These patients are particularly sensitive to treatment with an EGFR TKI which blocks the cell-signaling pathways that drive the growth of tumor cells.[10]

MET is a tyrosine kinase receptor.[11] Aberration of MET (amplification or overexpression) is present in both treatment naïve patients as well as being one of the primary mechanisms of acquired resistance to EGFR TKIs for metastatic EGFR-mutated NSCLC. [12],[13]

About Savolitinib (ORPATHYS in China)
Savolitinib is an oral, potent, and highly selective MET TKI that has demonstrated clinical activity in advanced solid tumors. It blocks atypical activation of the MET receptor tyrosine kinase pathway that occurs because of mutations (such as exon 14 skipping alterations or other point mutations) or gene amplification.

Savolitinib is marketed in China under the brand name ORPATHYS for the treatment of patients with NSCLC with MET exon 14 skipping alterations who have progressed following prior systemic therapy or are unable to receive chemotherapy. It is currently under clinical development for multiple tumor types, including lung, kidney, and gastric cancers, as a single treatment and in combination with other medicines.

In 2011, following its discovery and initial development by HUTCHMED, AstraZeneca and HUTCHMED entered a global licensing agreement to jointly develop and commercialize savolitinib. Joint development in China is led by HUTCHMED, while AstraZeneca leads development outside of China. HUTCHMED is responsible for the marketing authorization, manufacturing and supply of savolitinib in China. AstraZeneca is responsible for the commercialization of savolitinib in China and worldwide. Sales of savolitinib are recognized by AstraZeneca.

Savolitinib development in NSCLC
Phase II study of savolitinib monotherapy in MET Exon 14 skipping alteration NSCLC (NCT02897479) – In June 2021, savolitinib was granted drug registration conditional approval by the National Medical Products Administration of China (NMPA) for MET Exon 14 skipping alteration NSCLC. The approval was based on the results of a Phase II study in China; results of this study were published in The Lancet Respiratory Medicine[14]. At a median follow up of 17.6 months, savolitinib demonstrated an ORR of 42.9% (95% confidence interval [CI] 31.1-55.3) and median PFS of 6.8 months (95% CI 4.2-9.6) in the overall trial population. DCR in the overall trial population was 82.9% (95% CI 72.0-90.8). The safety and tolerability profile of savolitinib was consistent with previous trials, and no new safety signals were identified. Continued approval is contingent upon the successful completion of a confirmatory trial in this patient population (NCT04923945).

TATTON Phase Ib/II expansion studies of savolitinib in combination with TAGRISSO in patients who have progressed following EGFR TKI treatment due to MET amplification (NCT02143466) – This global exploratory study in over 220 EGFR mutation positive NSCLC patients with MET amplified tumors following progression after treatment with any EGFR TKI. Results were published in Lancet Oncology[15] and final analysis was presented at the World Conference on Lung Cancer[16]. Three cohorts with patients treated following progression on first- or second-generation EGFR TKI demonstrated an ORR of 64.7-66.7% and a median PFS of 9.0-11.1 months. The cohort of patients treated following progression on a third-generation EGFR TKI demonstrated an ORR of 33.3% (95% CI 22.4-45.7), with a median PFS of 5.5 months (95% CI 4.1-7.7). The combination demonstrated encouraging anti-tumor activity and an acceptable risk-benefit profile.

SAVANNAH Phase II study of savolitinib in combination with TAGRISSO in patients who have progressed following TAGRISSO due to MET amplification or overexpression (NCT03778229) – This is a single-arm, open-label, global study in epidermal growth factor receptor ("EGFR") mutation positive NSCLC patients with MET amplified/overexpressed tumors following progression after treatment with TAGRISSO, an EGFR TKI owned by AstraZeneca.

SACHI Phase III study of savolitinib in combination with TAGRISSO in patients who have progressed following EGFR TKI treatment due to MET amplification (NCT05015608) – This is a randomized, open-label study in China in EGFR mutation positive NSCLC patients with MET amplified tumors following progression after treatment with any EGFR TKI.

SANOVO Phase III study of savolitinib in combination with TAGRISSO in treatment-naïve patients with EGFR mutant positive NSCLC with MET overexpression (NCT05009836) – This is a randomized, blinded study in China in untreated, unresectable or metastatic patients with EGFR mutation positive NSCLC with MET positive tumors.

Savolitinib development in kidney cancer
SAVOIR randomized, controlled study of ORPATHYS monotherapy in MET-driven papillary renal cell carcinoma ("RCC") (NCT03091192) – In May 2020, data from 60 patients in this global study of savolitinib monotherapy compared with sunitinib monotherapy in MET-driven papillary RCC was presented at the ASCO (Free ASCO Whitepaper) 2020 Program and published simultaneously in JAMA Oncology[17]. Savolitinib demonstrated encouraging activity, including an ORR of 27% versus 7% for sunitinib, with no savolitinib responding patients experiencing disease progression at data cut-off, and an encouraging OS hazard ratio of 0.51 (95% CI: 0.21–1.17; p=0.110) with median not reached at data cut-off.

CALYPSO Phase I/II study of savolitinib in combination with IMFINZI PD-L1 inhibitor in RCC (NCT02819596) – The CALYPSO study is an investigator initiated open-label Phase I/II study of savolitinib in combination with IMFINZI, a PD-L1 antibody owned by AstraZeneca. The study is evaluating the safety and efficacy of the savolitinib /IMFINZI combination in patients with papillary RCC and clear cell RCC. An analysis of 41 patients enrolled in the PRCC cohort of in this study was presented at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting[18], showing a confirmed response rate in 8 out of 14 MET-driven patients, or 57%, with a median DoR of 9.4 months, median PFS of 10.5 months and median OS of 27.4 months. No new safety signals were seen.

SAMETA Phase III study in combination with IMFINZI PD-L1 inhibitor in MET-driven, unresectable and locally advanced or metastatic PRCC (in planning) – Based on the encouraging results of the SAVOIR and CALYPSO studies, we are planning to initiate SAMETA, a global Phase III, open-label, randomized, controlled study of savolitinib plus IMFINZI versus sunitinib monotherapy versus IMFINZI monotherapy in patients with MET-driven, unresectable and locally advanced or metastatic PRCC.

Savolitinib development in gastric cancer
Phase II study of savolitinib monotherapy in advanced or metastatic MET amplified gastric cancer ("GC") or adenocarcinoma of the gastroesophageal junction ("GEJ") (NCT04923932) – This is an open-label, two-cohort, multi-center study to evaluate the efficacy, safety and pharmacokinetics (PK) of savolitinib in locally advanced or metastatic GC or GEJ patients whose disease progressed after at least one line of standard therapy.

Savolitinib development in other cancer indications
Savolitinib opportunities are also continuing to be explored in multiple other MET-driven tumor settings via investigator-initiated studies including colorectal cancer.

About TAGRISSO
TAGRISSO is a third-generation, irreversible EGFR TKI with clinical activity against central nervous system metastases. TAGRISSO (40mg and 80mg once-daily oral tablets) has been used to treat more than 325,000 patients across indications worldwide and AstraZeneca continues to explore TAGRISSO as a treatment for patients across multiple stages of EGFR-mutated NSCLC.

In Phase III trials, TAGRISSO is being tested in the neoadjuvant resectable setting (NeoADAURA), in the Stage III locally advanced unresectable setting (LAURA) and, in combination with chemotherapy, in the Stage III locally advanced or Stage IV metastatic settings (FLAURA2). AstraZeneca is also researching ways to address tumor mechanisms of resistance through the SACHI and SANOVO Phase III trials, as well as the SAVANNAH and ORCHARD Phase II trials, which test TAGRISSO given concomitantly with savolitinib, as well as other potential new medicines.

On September 8, 2021 Clarity Pharmaceuticals (ASX: CU6) ("Clarity" or the "Company"), is an Australian-based clinical stage radiopharmaceutical company developing next-generation products to address the growing need for the use of radiopharmaceuticals in oncology (Press release, Clarity Pharmaceuticals, SEP 8, 2021, View Source [SID1234587369]). The Company commences trading on the Australian Securities Exchange (ASX) at 11:00am (Sydney, Australia time) today following the completion of an initial public offering (IPO).

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The IPO raised $92.0 million and was strongly supported by institutional, professional and retail investors. Jefferies (Australia) Pty Ltd and Bell Potter Securities Limited were Joint Lead Managers and Underwriters to the IPO.

Clarity is a global leader in Targeted Copper Theranostics (TCT), developed with its proprietary SAR Technology platform. TCT are the next-generation disruptive platform in radiopharmaceuticals that employ the "perfect pairing" of copper-64 (64Cu) and copper-67 (67Cu) for diagnosis and therapy respectively. TCT deliver a compelling combination of high accuracy and high precision in the treatment of a range of cancers, as well as providing supply and logistical advantages over current radiopharmaceuticals. TCT provide a highly efficacious, scalable, and cost-effective way to expand radiopharmaceuticals into the global oncology market.

Clarity’s proprietary SAR Technology platform can be used to develop a range of theranostic radiopharmaceuticals that target different types of cancer. At the heart of Clarity’s theranostic SAR Technology platform is a highly specific and highly stable bifunctional chelator (cage) that strongly binds and retains copper isotopes within it. The cage is linked to a targeting molecule, which finds and binds tumour specific receptors on cancer cells. Together with the targeting molecule and the isotope, the technology enables the development of radiopharmaceuticals for diagnosis and therapy in oncology.

Clarity has a diverse range of products in clinical trials which address both large indications (prostate cancer and breast cancer) as well as rare and orphan indications (neuroendocrine tumours (NETs) and neuroblastoma) of cancer, thereby positioning the products to take advantage of the high unmet needs that currently exist in respect of the medical treatment used for these types of cancers. The products in the clinical stage of development include:

SARTATE: for the treatment of neuroblastoma, Phase I/IIa; for the diagnosis of neuroendocrine tumours (NETs), Phase II;
SAR-Bombesin: a pan-cancer treatment product, including for the treatment of breast cancer and prostate cancer, Phase I; and
SAR-bisPSMA: for the treatment of prostate cancer, Phase I/IIa; for the diagnosis of prostate cancer, Phase I.
Clarity’s focus in the clinical development process is on high quality clinical sites and experienced investigators. The Company is targeting the lucrative US market for first product approvals and expects that it will have sufficient cash to fund its medium-term operational requirements and business objectives as a result of the funds raised under the IPO.

Clarity is led by a management team and Board who possess a diverse range of skills and expertise, together with

extensive experience in the radiopharmaceutical market. Alongside the management team and Board, Clarity has a Scientific Advisory Board, which consists of key opinion leaders who have significant research and clinical experience in global radiopharmaceuticals.

Clarity’s Executive Chairman, Dr Alan Taylor, commented: "Our Board and management team are committed to our strategy. We believe Clarity to be a global leader in targeted copper theranostics with best-in-class chelator technology. The IPO significantly advances our business and we are delighted to welcome our new shareholders and thank our existing shareholders for their continued support.

"Our proprietary SAR Technology platform addresses the growing need for the use of radiopharmaceuticals in oncology and we believe that targeting the US market for first clinical approvals will assist in potentially achieving large scale market penetration of our products.

"We look forward to continuing to grow the business, deliver on our strategy and move closer to our ultimate goal of developing better treatments for children and adults with cancer."

On September 8, 2021 Cernostics, pioneer of the worlds’ first precision medicine test to predict future development risk of esophageal cancer from Barrett’s esophagus (BE), TissueCypher Barrett’s Esophagus Assay, reported that it has become a participating ("in- network") provider for Geisinger Health Plan (GHP)’s more than 550,000 plan members in Central, North Central and East Central Pennsylvania (Press release, Cernostics, SEP 8, 2021, View Source;utm_medium=rss&utm_campaign=cernostics-contracts-with-geisinger-health-plan-to-become-an-in-network-provider-for-tissuecypher-barretts-esophagus-assay [SID1234587389]). The TissueCypher Barrett’s Esophagus Assay has been a covered service for GHP members since a January 2021 decision determined that it was "medically necessary" for the evaluation of biopsies from certain BE patients, becoming the first commercial health care plan to have a coverage policy for TissueCypher.

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This decision by GHP comes in response to multiple recent peer-reviewed publications that independently validated the clinical validity and clinical utility of the TissueCypher Barrett’s Esophagus Assay.

Objectively and accurately predicting progression from BE to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) is critical as the incidence of esophageal cancer is growing in the US at one of the fastest rates of all cancers. Once diagnosed, EAC is highly lethal, so early detection and advanced warning in patients with BE by TissueCypher provides valuable clinical decision support to physicians managing these patients.

"We’ve collaborated with Cernostics in the development of the clinical evidence demonstrating the value of TissueCypher for risk-stratification of patients with BE. TissueCypher uses biomarker information not available by any other technology and has allowed us to determine optimal treatment and follow-up strategies in an informed and intelligent way. Importantly, the test can be run on previously obtained biopsies. It’s exciting to see that our patients and gastroenterologists now have access to this important technology as a covered benefit and in-network lab service," said Dr. David Diehl, Director of Interventional Endoscopy at Geisinger Medical Center.

Mike Hoerres, Chief Executive Officer of Cernostics, added, "We are proud to work with Geisinger, one of the leading integrated healthcare delivery systems in the US, to bring TissueCypher testing to our neighbors throughout Pennsylvania. We see this as a great way to support the legacy and vision of Abigail Geisinger, delivering state-of-the-art medicine to the communities we serve right here in Pennsylvania."