On September 20, 2021 miR Scientific reported that Data presented from a cross-validation study at the American Urological Association’s (AUA) 2021 Annual Meeting confirms that the miR Sentinel Prostate Cancer Test can detect and risk-classify prostate cancer at the molecular level with predictive accuracy of over 90%, based on a single urine sample (Press release, miR Scientific, SEP 20, 2021, View Source [SID1234588048]). This validation study follows and confirms the data on more than 1,400 patients published in The Journal of Urology in September 2020.

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When comparing the results of the miR Sentinel Prostate Cancer Test to systematic core needle biopsy in men presenting with initial suspicion of prostate cancer, the latest validation study demonstrated a 93% concordance between the two methods of screening and detection regarding the classification of clinically significant cancer. This 93% sensitivity of the miR Sentinel Prostate Cancer Test sets a new bar for detecting and classifying prostate cancer. The data further demonstrate the strong negative predictive value of the miR Sentinel Prostate Cancer Test with results showing the test correctly identified 96% (371/387) of men as having non-clinically significant cancer.

"Our mission to inclusively transform cancer management is further validated in this prospective study, demonstrating that the miR Sentinel Prostate Cancer Test is able to provide an accurate non-invasive means to identify the presence or absence of any prostate cancer and classify the molecular risk of disease becoming metastatic, and thereby lethal, prior to biopsy" says Sam Salman, Chairman and CEO of miR Scientific. "We believe that the accuracy, accessibility, and non-invasive features of our award-winning technology will impact the lives of millions of men and forever positively evolve the standard of care for urological cancers."

Cross-Validation Study Results

The data reported in this late-breaking abstract and presented by Laurence Klotz, MD, FRCSC at the AUA, is based on a study of 763 men over 45 years old, eligible for their first core needle biopsy. Pathology based on the core needle biopsy showed 354 (46%) were biopsy negative and 409 (54%) were biopsy positive. Of those 409 men found to have pathologic evidence of disease, 189 (25%) were classified as Grade Group 1 (GG1) representing non-clinically significant cancer, and 220 were classified as Grade Group 2 (GG2) or higher representing clinically significant cancer.

With just a urine liquid biopsy, the miR Sentinel Prostate Cancer Test identified 204 men with clinically significant cancer (intermediate or high risk), demonstrating 93% sensitivity (204/220) with the core needle biopsy. When evaluating men with non-clinically significant cancer, the miR Sentinel Prostate Cancer Test identified 371 out of 387 men, delivering 96% (371/387) sensitivity.

The data further examined the apparent false positive rate for clinically significant cancer by analyzing the sub-set of men who underwent both systematic biopsy and MRI-fusion biopsy, and who were negative on systematic biopsy. The data demonstrates >95% concordance been the positive MRI-guided biopsy and the miR Sentinel Prostate Cancer Test, indicating that the discordance between systematic biopsy results and the miR Sentinel Prostate Cancer Test are largely attributable to false negatives of biopsy.

Laurence Klotz, MD, FRCSC, Professor of Surgery at the University of Toronto, and Chief Medical Officer of miR Scientific LLC, said, "The key features of the test are the very high negative predictive value and the very high accuracy [in] identifying cancer. In addition to its quick turnaround, the test is highly scalable: the company will be able to perform a very large number of these tests right away."

Innovative Urine-based Liquid Biopsy

The miR Sentinel Prostate Cancer Test, which already received the Breakthrough Device Designation by the FDA, is a non-invasive molecular test based on the analysis of small non-coding RNAs (sncRNA) isolated from non-DRE urinary exosomes. It provides an innovative method to analyze sncRNAs derived from a simple, non-invasive urine specimen from age-eligible men. Using only the expression dynamics of these sncRNAs, a proprietary Statistical Classification Algorithm derives scores that classify patients according to the likelihood of being in the following four possible groups: no molecular evidence of prostate cancer; low-risk; intermediate-risk; or high-risk prostate cancer.

The miR Sentinel Prostate Cancer Test is expected to be commercially available in the United States and Puerto Rico at the end of this year.

On September 20, 2021 Alvotech, a multinational biopharmaceutical company focused on the development and manufacturing of high quality biosimilars for global markets, reported that the FDA is deferring action on the application for AVT02, the company’s proposed biosimilar to Humira, until facility assessments can be completed (Press release, Alvotech, SEP 20, 2021, View Source [SID1234588041]). The FDA can defer action1 when no deficiencies have been identified and the application otherwise satisfies the requirements for approval, but an inspection(s) is necessary yet cannot be completed due to factors including travel restrictions. Alvotech continues to work with the FDA to coordinate the required inspection(s) in a safe and adequate manner.

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Alvotech is the only known company that has both submitted a Biologics License Application(BLA) for a high-concentration biosimilar candidate to Humira, the most commonly utilized strength of the product on the market, and has successfully conducted a switching study in support of an FDA designation of interchangeability and correspondingly the potential for product substitution at the pharmacy level. Teva Pharmaceuticals, a U.S. affiliate of Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) is the exclusive strategic partner for the commercialization of AVT02 in the United States.

In addition to the positive top-line results seen in the switching study, Alvotech on Sept. 16, 2021 received a positive opinion from the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) recommending the approval of AVT02 in the EU. The European Commission (EC) will consider the CHMP’s positive opinion when deciding to grant a marketing authorization for AVT02 at its October meeting.

The Biden Administration and the U.S. Department of Health and Human Services (HHS) have expressed support for the increased competition and healthcare savings generated by biosimilars and interchangeable biosimilars.

"The U.S. Government has made it clear that increasing the affordability of prescription drugs, through enhanced competition in biologic medicines, is a significant priority," said Mark Levick, CEO of Alvotech. Adding, "We strongly share the view that biosimilar medicines and interchangeable biosimilars present a unique opportunity to contribute to improving equity in healthcare"

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On September 20, 2021 Xilis, Inc., a pioneering company developing its MicroOrganoSphereTM (MOS) technology to guide precision therapy for cancer patients and accelerate drug discovery and development, reported the presentation of data on the company’s proprietary MOS technology (Press release, Xilis, SEP 20, 2021, View Source [SID1234588037]). Data were presented at the 2021 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress in an oral presentation and two poster presentations.

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"There is a significant unmet need for a patient-derived microtumor platform that captures the entire microenvironment and heterogeneity of the originating tumor tissue for accurate, rapid and high-throughput therapeutic profiling," said Xiling Shen, PhD, Founder and Chief Executive Officer of Xilis. "In these three presentations, we provide evidence that our MOS technology retains the same characteristics as patient samples and has the capability to quickly evaluate cancer drug response. Our platform can support pharmaceutical companies in accelerating drug discovery and development and is being developed to help clinicians make more informed treatment decisions."

"Patient-derived MicroOrganoSpheres Recapitulate Tumor Microenvironment and Heterogeneity for Precision Oncology"

Data from the oral presentation highlighted Xilis’ automated microfluidic platform to generate tens of thousands of MOS from resected or biopsied clinical tumor specimens. The studies showed that MOS could be derived from four primary cancer tissue types (colorectal cancer, lung tumor, breast tumor and kidney tumor), while retaining the genomic, transcriptomic and stromal features of the parent tissue. Additionally, we demonstrated that PD-1 immunotherapy activated tumor-infiltrating lymphocytes (TILs) within the MOS and induced cell death.

"MicroOrganoSpheres as a Novel Precision Oncology Platform in Colorectal Cancer"

In the MicroOrganoSphere Drug Screen to Lead Care (MODEL) proof-of-concept clinical trial, results from the poster presentation demonstrated that MOS technology could be used as a potential therapeutic diagnostic assay to help guide treatment strategies for metastatic colorectal cancer. In less than 14 days after individual patient tumor tissue were biopsied, MOS were generated and established followed by drug screening to predict each patient’s sensitivity or resistance to oxaliplatin. With results generated in less than two weeks, these studies are a significant step towards showing that MOS can be used to correlate drug response to clinical outcomes and supports future validation in clinical trials.

"MicroOrganoSphereTM: An Automated Platform for Rapid Drug Screening in Patient-Derived Breast Cancer Organoids"

Data from the poster presentation showed a positive correlation in breast cancer drug response for 10 FDA-approved therapies between MOS, conventional bulk organoids and patient-derived xenografts. Breast cancer MOS were established as early as 2-3 days and continued to grow over seven days while maintaining the genomic features of the parent tissue. These studies demonstrate that Xilis’ MOS technology can be utilized to evaluate drug sensitivities in high-throughput screening for drug discovery and once validated, offer guidance in patient treatment planning.

Presentations are available on the Xilis website.

On September 20, 2021 Xencor, Inc. (NASDAQ:XNCR), a clinical-stage biopharmaceutical company developing engineered monoclonal antibodies and cytokines for the treatment of cancer and autoimmune diseases, reported that company management will present at the Cantor Virtual Global Healthcare Conference on Monday, September 27, 2021 at 4:00 p.m. ET / 1:00 p.m. PT (Press release, Xencor, SEP 20, 2021, View Source [SID1234588033]).

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A live webcast will be available under "Events & Presentations" in the Investors section of the Company’s website located at www.xencor.com. Following the webcast, a replay will be archived on the website for at least 30 days.

On September 20, 2021 Syros Pharmaceuticals (NASDAQ:SYRS), a leader in the development of medicines that control the expression of genes, reported new data from the dose-escalation portion of the Phase 1 clinical trial of SY-5609, its highly selective and potent oral cyclin-dependent kinase 7 (CDK7) inhibitor, demonstrating clinical activity at tolerable doses as a single agent across multiple tumor types (Press release, Syros Pharmaceuticals, SEP 20, 2021, View Source [SID1234588030]). The data is being presented today in an oral presentation at the 2021 ESMO (Free ESMO Whitepaper) Congress.

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"I am encouraged by the results from this dose-escalation study," said Manish R. Sharma, M.D., Associate Director of Clinical Research at START Midwest in Grand Rapids, Michigan, and an investigator in the Phase 1 study of SY-5609. "This trial enrolled heavily pretreated patients with some of the most difficult-to-treat malignancies. Notably, the prolonged stable disease and tumor shrinkage seen in pancreatic cancer patients is distinct from what you would expect to see in this highly refractory patient population – particularly when treated with a single agent. Based on these results, together with preclinical data supporting combination strategies, I believe SY-5609 has the potential to provide a meaningful benefit for patients with cancers that have largely eluded treatment to date."

"The new data presented today demonstrate proof-of-activity for SY-5609 and point to an optimal dosing regimen with a tolerability profile that is amenable to multiple combination approaches," said David A. Roth, M.D., Chief Medical Officer of Syros. "As we move into this next stage of development, we are introducing a three-pronged strategy to maximize the potential of SY-5609 and drive to proof-of-concept in combination with chemotherapy, a targeted therapy and an immunotherapy in both solid tumors and blood cancer. We believe this approach could unlock significant opportunities for SY-5609 and achieve the transformative potential of CDK7 inhibition for people with difficult-to-treat cancers."

Dose-Escalation Data Demonstrate Clinical Activity Across Multiple Tumor Types
The Phase 1 multi-center, open-label dose-escalation study of SY-5609 enrolled patients with advanced breast, colorectal, lung, ovarian and pancreatic cancers, as well as patients with solid tumors of any histology harboring Rb pathway alterations. Patients were treated in cohorts exploring continuous daily dosing as well as intermittent dosing regimens, including seven days on treatment and seven days off (7d on/7d off) and five days on treatment and two days off (5d on/2d off).

As of July 6, 54 patients treated with single-agent SY-5609 in the study were eligible for a safety analysis and 45 patients were evaluable for clinical response. The median age of patients enrolled in the study was 65.5. Patients had been heavily pre-treated with as many as eight prior therapies and a median of four prior therapies.

Safety, Tolerability, Dose and Schedule

Across all doses and schedules, the majority of adverse events (AEs) were low-grade and reversible. The most common treatment-emergent AEs were nausea, diarrhea, thrombocytopenia, fatigue and anemia.
Low rate of discontinuations due to AEs.
Tolerability was optimized with 7d on/7d off schedule, which had lowest rates of treatment-emergent AEs, while demonstrating comparable rates of stable disease (SD) as seen with more dose-intense regimens, supporting the selection of this schedule for further development of SY-5609.
The maximum tolerated dose (MTD) of the 7d on/7d off schedule has not yet been reached.
Changes in POLR2A mRNA expression, a pharmacodynamic (PD) marker for CDK7 inhibition, were associated with anti-tumor activity and were sustained for at least three days following drug cessation, supporting intermittent dosing.
Early Clinical Activity Data

Thirteen patients (28.9%) achieved SD, with tumor regressions of up to 20% in six of those patients, across multiple tumor types.
The most substantial clinical activity was observed in heavily pre-treated patients with advanced pancreatic cancer.
Five of 13 (38.5%) evaluable patients achieved SD, with tumor reductions in two of those patients.
Reductions in the CA 19-9 tumor marker, which is used in clinical practice to monitor tumor progression, were observed in three of four pancreatic cancer patients with serial CA 19-9 data. These reductions ranged from 32% to 72%.
Notably, one metastatic pancreatic cancer patient who had failed two prior lines of therapy and relapsed after a third line of treatment experienced prolonged SD of up to 10 months.
Analysis of clinical activity by tumor type and mutational status supports the mechanistic rationale for SY-5609 in Rb-altered and KRAS-mutant cancers.
Clinical Development Plans for SY-5609 in Solid Tumors and Blood Cancer
Further development of SY-5609 will explore three combination regimens, focusing initially on indications with compelling clinical and/or preclinical activity, as well as a strong mechanistic rationale and high unmet need.

Syros plans to initiate an expansion cohort evaluating SY-5609 in combination with chemotherapy for the treatment of pancreatic cancer in the fourth quarter of 2021. Syros also plans to initiate a Phase 1b trial evaluating SY-5609 in combination with a Bruton’s tyrosine kinase (BTK) inhibitor for the treatment of mantle cell lymphoma in the first half of 2022. Syros plans to employ a 7d on/7d off dosing schedule in both of these trials. In addition, as announced in August 2021, Syros entered into an agreement with Roche to explore SY-5609 in combination with atezolizumab in patients with BRAF-mutant colorectal cancer in Roche’s ongoing Phase 1/1b INTRINSIC trial.

New Preclinical Data Further Support Planned Expansion Strategy
Syros also presented new preclinical data at ESMO (Free ESMO Whitepaper) evaluating the anti-tumor and PD activity of intermittent dosing regimens for SY-5609, as well as new preclinical data evaluating SY-5609 as a single agent and in combination with chemotherapy in pancreatic cancer models. Taken together, these data further support Syros’ dose expansion strategy, including the decision to use a 7d on/7d off dosing schedule and combine with chemotherapy in patients with pancreatic cancer. The data showed that SY-5609:

Induced robust anti-tumor activity as a single agent in ovarian cancer models that was maintained at higher doses on intermittent schedules, including a 7d on/7d off schedule. POLR2A PD effects were sustained in tumor tissue through 72 hours post-dosing, consistent with what was observed in patients in the dose-escalation study.
Induced regressions as a single agent in half (4/8) of the pancreatic cancer models that were studied, including models derived from heavily pre-treated patients.
Resulted in deeper responses when combined on 7d on/7d off schedule with gemcitabine in KRAS-mutant pancreatic models than either agent alone.
Conference Call Information
Syros will host a conference call at 4:00 p.m. ET today to discuss these data, as well as the design of its dose expansion study. To access the live conference call, please dial 866-595-4538 (domestic) or 636-812-6496 (international), and refer to conference ID 4648345. A webcast of the call will also be available on the Investors & Media section of the Syros website at www.syros.com. An archived replay of the webcast will be available for approximately 30 days following the conference call.