On November 12, 2021 Biodesix, Inc. (Nasdaq: BDSX), a leading data-driven diagnostic solutions company with a focus in lung disease, reported that the company will co-present with Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), three posters at the 36th Annual Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Nov. 10 – 14, 2021 from research into diagnostic tests of treatment response of NSCLC patients to immune checkpoint inhibitor therapy (Press release, Biodesix, NOV 12, 2021, View Source [SID1234595467]).

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"Biodesix is committed to performing research with biopharma companies, while pursuing, discovering and developing applications that can help physicians and researchers address the needs of patients with lung cancer who will benefit from quick, actionable test results," said Scott Hutton, CEO, Biodesix. "We are pleased to present data on two tests that have the potential to become instrumental in the care of patients with non-small cell lung cancer (NSCLC). Additionally, our data highlights novel methods that we have developed to provide an explanation as to how our proprietary Diagnostic Cortex Artificial Intelligence (AI) platform combines molecular attributes to produce individual patient results. This data is extremely important because we expect that this will provide clarity and transparency to how our AI-based tests work and how a diagnostic test may better predict efficacy of various treatments in the most appropriate patient populations. We are proud of the data being presented at SITC (Free SITC Whitepaper) as it underscores our commitment to the lung cancer community."

The three Genentech/Biodesix-sponsored posters include the following:

Abstract #26: Validation of the Primary Immune Response (PIR) test in advanced non-small cell lung cancer (NSCLC): blinded retrospective analyses from the POPLAR and OAK trials

Findings will be presented from blinded, retrospective analyses of two Genentech multicenter, open-label RCT clinical studies comparing atezolizumab versus docetaxel in patients with previously treated NSCLC (POPLAR Phase 2 and OAK Phase 3). The Biodesix liquid-biopsy mass spectrometry-based Primary Immune Response (PIR) test stratified outcomes for patients treated with the study drug in second and third line, predicting overall survival, even when adjusted for PD-L1 expression and clinical factors. The importance of understanding who will or will not respond to immunotherapy is critical and identifying predictive biomarkers of immunotherapy response has become a growing focus of immune-oncology research. This study highlights the potential of biomarkers of immune checkpoint inhibitors, such as the PIR test, to support patient stratification.

Abstract #28: Predictions of outcomes and benefit of immune checkpoint inhibitor treatment in non-small cell lung cancer require information on both tumor and host biology

Findings from a Genentech blinded, retrospective study of second- and third-line NSCLC patients in the OAK Phase 3 clinical study comparing atezolizumab versus docetaxel in patients with previously treated NSCLC will be presented. The study demonstrated that the Biodesix Anti-PD-L1 Response Test (ART), based on mass spectrometry of pretreatment serum, stratifies outcomes in both treatment arms overall and in all PD-L1 subgroups. The Biodesix ART test was shown in independent validation to predict outcomes for NSCLC patients treated in a large Phase 3 study and was discovered and developed for Genentech as a part of a partnership between the two companies.

Abstract #831: Exact Shapley Values for explaining complex machine learning based molecular tests of checkpoint inhibitors: potential utility for patients, physicians, and translational research

Data will show how Exact Shapley Values (SVs), a technique developed by Biodesix, can explain how complex machine learning (ML)-based tests combine molecular attributes to produce individual patient results. Exact SVs can be obtained for certain ML architectures used in molecular test development, revealing the overall relative importance of attributes used in such molecular tests. Specifically, this study evaluated SVs for the Biodesix Anti-PD-L1 Response Test (ART), that was shown in independent validation to predict outcomes for NSCLC patients treated in a large Phase 3 study. By subgrouping patients according to ART results, different patterns of SVs were determined, potentially revealing different biologies that were predictive of overall survival outcomes. Exact SVs explain how complex ML-based tests combine molecular attributes to produce individual patient results.

On November 12, 2021 PathAI, a global provider of AI-powered technology applied to pathology reported that results from a recent exploratory biomarker analysis on digitized slides to apply AI-predicted CD8 topology assessment of patients with advanced melanoma will be presented at the annual Meeting of Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), November 10-14 2021 (Press release, PathAI, NOV 12, 2021, View Source [SID1234595483]).

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The results will be shared in two posters, Lee et al. The utility of AI-powered spatial classification of intratumoral CD8+ immune-cell topology in predicting overall survival in patients with melanoma as part of the CheckMate 067 clinical trial, and Glass et al. Machine Learning Models Can Quantify CD8 Positivity in Melanoma Clinical Trial Samples.

PathAI developed Machine Learning (ML) models to quantify CD8+ T cells in digitized whole slide images (WSI) of melanoma patient samples, and validated their performance against a consensus of pathologists on a held-out data set. These models were deployed on CD8-stained biopsy samples collected from patients with previously untreated advanced melanoma in the CheckMate 067 clinical trial. The AI-based predictions of CD8 positivity were used by ML models created by Bristol Myers Squibb to categorize each WSI by spatial pattern and density of CD8+ T cell infiltration (CD8 topology) as desert (deficient in CD8+ T cells), excluded (CD8+ T cells at the tumor boundaries and surrounding stroma), or inflamed (CD8+ T cells within the tumor parenchyma).

PD-L1 stained tumor cell positivity scores of either PD-L1 <1% or PD-L1 >1%, collected previously during the CheckMate 067 clinical trial, were combined with the CD8+ spatial phenotype scores to create a composite biomarker. Correlations between overall survival of patients in CheckMate 067 and CD8+ spatial phenotype alone, or the composite biomarker identified a subpopulation of patients with PD-L1 expression < 1%, and a CD8+-excluded tumor spatial pattern that benefited significantly from the drug combination treatment (nivolumab and ipilimumab) compared with PD-L1 negative patients with a CD8+-inflamed tumor spatial pattern (P = 0.002). No difference in survival between excluded and inflamed phenotypes was observed for patients treated with monotherapy (nivolumab alone) (P = 0.41), nor with any patients with PD-L1 >1%.

The data presented here suggest that in addition to PD-L1 positive patients, PD-L1 negative CheckMate 067 patients who were also CD8+ in specific subregions of tumors had overall survival benefit when treated with ipilimumab plus nivolumab combinations compared to those that were treated with ipilimumab monotherapy.

Together, these publications highlight the promise of ML-based CD8+ phenotype scoring to reveal populations of patients that might have the greatest benefit from existing treatments.

On November 12, 2021 Sosei Group Corporation ("the Company") (TSE: 4565) reported that in AstraZeneca’s third quarter 2021 clinical trials appendix presentation (published today and available on www.astrazeneca.com), the oral, small molecule adenosine A2a receptor antagonist imaradenant (AZD4635) has been removed from its clinical development pipeline as part of its ongoing pipeline prioritization (Press release, Sosei Heptares, NOV 12, 2021, View Source [SID1234595499]). Imaradenant was discovered by Sosei Heptares and licensed to AstraZeneca in 2015.

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AstraZeneca has been evaluating imaradenant in Phase 1 and 2 clinical trials as a monotherapy and in combination with Imfinzi (durvalumab) in solid tumors. In these trials, imaradenant, with or without Imfinzi, was found to be safe and well tolerated and associated with clinical benefit in some immune checkpoint-naïve patients with metastatic castrate-resistant prostate cancer (mCRPC). Imaradenant has been extensively tested in patients with a range of different solid tumor types and has been demonstrated to be safe and well tolerated at escalating doses.

Targeting the production or action of adenosine is a promising strategy for overcoming immune suppression in the tumor microenvironment, and several companies have now disclosed positive results from early clinical trials.

AstraZeneca has a diverse oncology pipeline that requires it to regularly make strategic prioritization decisions regarding projects in its portfolio. Following the removal of the imaradenant program from AstraZeneca’s clinical pipeline, Sosei Heptares will discuss with its partner AstraZeneca the next steps for the future of imaradenant, including the possibility of the Company regaining worldwide rights to the licensed program.

The event reported today has no material impact on the consolidated financial results for the fourth quarter and full year accounting period ending 31 December 2021. Should any impacts or other matters that require an announcement be identified, the Company will announce such matters promptly.

Shinichi Tamura, President and CEO of Sosei Heptares, commented: "The imaradenant clinical program has generated encouraging clinical results in cancer patients under AstraZeneca’s guidance. We respect their decision on imaradenant, as a result of a pipeline portfolio review, and we are keen to assess the possibility of regaining the worldwide rights in order to evaluate the future clinical development and/or re-licensing potential of the program, as we have successfully done so on multiple occasions. AstraZeneca is one of our longest serving partners, and we have enjoyed a highly productive collaboration with them. We look forward to the ongoing discussions about the future of imaradenant and will report the outcome in due course."

On November 12, 2021 Curaleaf Holdings, Inc. (CSE: CURA / OTCQX: CURLF) ("Curaleaf" or the "Company"), a leading international provider of consumer products in cannabis, reported that entered into a definitive agreement to acquire Tryke Companies ("Tryke") (dba as Reef Dispensaries), a privately held vertically integrated, multi-state cannabis operator, in a cash and stock transaction valued at approximately US$286 million (Press release, Curaleaf Holdings, NOV 12, 2021, View Source [SID1234595546]).1 The transaction is expected to close in the second half of 2022, subject to customary approvals and conditions.

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Under the terms of the agreement, Curaleaf will pay US$40 million in cash at closing, with a remaining US$75 million in cash to be paid in equal installments on the first, second and third anniversaries of the closing. The stock portion of the transaction, which consists of 17 million subordinate voting shares of Curaleaf ("Curaleaf Shares"), will also be paid in three equal installments on the first, second and third anniversaries of the closing. An incremental earnout of up to 1 million Curaleaf Shares may be paid in 2023 based on the business exceeding certain EBITDA targets for the year 2022.

Founded in Arizona in 2014, Tryke has focused on growing and producing the finest and most consistent cannabis products on the market. The company helped pioneer Nevada’s legal cannabis market from its inception in 2015, and continues to lead the industry in Utah where it has worked since 2019 to help establish the state’s medical cannabis program. Tryke has refined processes to craft an ever-evolving selection of products and brands at multiple price points. The company’s dispensaries have served more than 7.6 million customers, offering a wide variety of in-house and third-party flower, concentrates, vape cartridges, edibles, topicals and CBD products. Upon closing, Curaleaf will assume ownership of Tryke’s extensive portfolio of processing licenses and expects to significantly expand its cultivation capacity from 30,000 square feet to over 80,000 square feet over the next three years.

Boris Jordan, Founder and Executive Chairman of Curaleaf, said, "On Behalf of the Board of Directors and management team, I look forward to welcoming Tryke to the Curaleaf family as we expand our offerings and operations and bolster our competitive position in three key growth markets. We believe that Tryke represents a unique opportunity to join forces with another industry leading pioneer that shares Curaleaf’s commitment to legalization and expansion. This strategically and financially compelling transaction will expand our US presence by bringing additional premium products to our consumers and retailers in Nevada, Arizona and Utah, all while yielding meaningful benefits for all of our stakeholders. We expect the acquisition to be immediately accretive to our EBITDA margins and free cash flow generation upon closing."

1 Based on the closing price of Curaleaf’s subordinate voting shares on the OTC market as of November 5, 2021.

"This is a tremendous opportunity for Tryke and, as a combined entity, we will continue to deliver significant value for our consumers and retailers in Arizona, Nevada and Utah," said Adam Ryan, Chief Executive Officer of Tryke Companies. "As a part of Curaleaf’s growing network of dispensaries, Tryke is excited to bring its full suite of multi-price point products to an expanded base of consumers across the country. We are excited to join forces with the industry leader at such a pivotal moment in the United States’ legalization efforts. We share Curaleaf’s optimism for the future and are excited to become investors alongside the Company’s talented leadership team."

Compelling Strategic and Financial Benefits

·Enhances Curaleaf’s operations in Arizona, Nevada and Utah: Tryke currently owns and operates six heavily trafficked dispensaries under the Reef brand, with two retail stores in Arizona and four in Nevada, including the Phoenix metropolitan area, Las Vegas strip and North Las Vegas. The company’s products are sold in over 50 additional locations across its footprint.

·Enriches Curaleaf’s product offerings: Tryke currently offers a wide variety of in-house and third-party flower, concentrates, vape cartridges, edibles, topicals and CBD products at a range of price points. Tryke’s product portfolio is highly complementary to Curaleaf’s, allowing the Company to offer consumers and retailers in Arizona, Nevada and Utah an even broader selection of premium cannabis products.

Improves Curaleaf’s margins and free cash flow generation: Tryke has a strong financial profile, with a history of delivering significant revenue growth and compelling EBITDA margins in excess of 35%. Tryke is expected to record nearly US$110 million in full year 2021 revenue. Curaleaf expects the acquisition will be immediately accretive to the Company’s EBITDA margins and free cash flow generation.

The closing of the transaction is expected to occur in the second half of 2022 subject to customary closing conditions, including the receipt of approval from the applicable state regulators, including the Nevada Cannabis Compliance Board.

Transaction Advisors

In a separate press release to be issued today after the market closes, Curaleaf will announce its financial results for the third quarter of 2021, and it will be available at View Source

Conference Call & Webcast

Curaleaf will hold a conference call today, November 8, at 5:00 p.m. Eastern Time to discuss this announcement, as well as its third quarter 2021 results. Investors who wish to participate in the call should dial 1-888-317-6003 (U.S.) or 1-866-284-3684 (Canada) or 1-412-317-6061 (International) approximately 15 minutes before the call begins and provide conference ID number 2599473.

On November 12, 2021 Biosight Ltd., a pharmaceutical development company developing innovative therapeutics for hematological malignancies and disorders, reported the initiation of a Phase 2 trial to evaluate aspacytarabine (BST-236), Biosight’s proprietary antimetabolite, as a second line treatment for patients with relapsed or refractory myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) (Press release, Advaxis, NOV 12, 2021, View Source;soc_trk=ma [SID1234595728]). The multi-center study will be conducted across 18 leading U.S. and Israeli sites including Memorial Sloan Kettering Cancer Center and The University of Texas MD Anderson Cancer Center.

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"Biosight has built a strong foundation of compelling data that suggests that aspacytarabine may serve as a more tolerable and effective standard of care treatment for patients with AML," said Dr. Ruth Ben Yakar, Chief Executive Officer of Biosight. "The initiation of this multi-center, U.S. based, Phase 2 study is an important step forward in the development of aspacytarabine, seeking to address unmet needs in the treatment of patients with relapsed or refractory AML and MDS. We are proud to be continuing our momentum in the clinic and look forward to collaborating with leading academic medical centers as we progress the study."

Eytan Stein, M.D., Hematologic Oncologist at Memorial Sloan Kettering Cancer Center and lead investigator of the study said "I’m encouraged by the results from Biosight’s Phase 2b trial to be presented at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. The efficacy achieved in a challenging population, across key measures including complete remission and MRD (-) rates, duration of response and overall survival, are noteworthy. Furthermore, these results were particularly impressive as they were achieved with a favorable safety and tolerability profile in patients who are unfit for intensive chemotherapy. Patients with relapsed or refractory AML and MDS have limited treatment options and poor prognoses, with many patients unable to tolerate intensive chemotherapy. I look forward to leading this new Phase 2 study to evaluate the potential of aspacytarabine which may ultimately become the standard of care for relapsed or refractory MDS and AML patients for whom currently there are no effective treatments."

The Phase 2 open label multi-center study will assess the safety and efficacy of BST-236 as a single agent in adult patients unfit for standard therapy with AML or higher-risk (HR)MDS who fail to respond to, or have relapsed following, first line therapy. A similar study in patients with relapsed/refractory AML and MDS is ongoing in collaboration with the European cooperative group, Groupe Francophone des Myélodysplasies (GFM). Approximately 40 adult patients with relapsed and/or refractory AML and approximately 40 adult patients with relapsed and/or refractory HR MDS will be enrolled into the two studies. Primary endpoints include complete remission (CR) rate in AML patients and Overall Response Rate (ORR) in MDS patients, with ORR defined as the proportion of patients who achieve a CR or partial response (PR) per proposal for modification of the International Working Group (IWG) criteria for MDS, 2006.

About Aspacytarabine (BST-236)

Aspacytarabine is a novel proprietary anti-metabolite. It is composed of cytarabine covalently bound to asparagine, acting as a pro-drug of cytarabine. Cytarabine has served as the backbone of AML therapy for over 45 years due to its superior efficacy. However, it is associated with severe bone marrow, gastrointestinal, and neurological toxicities, which significantly limit its use, especially in older and medically compromised patients. Due to its unique pharmacokinetics and metabolism, aspacytarabine enables high-dose therapy with lower systemic exposure to free cytarabine and relative sparing of normal tissues. As such, aspacytarabine may serve as a new therapy for AML and other hematological malignancies and disorders, including for older adults who are unfit for intensive therapy.

Aspacytarabine was granted FDA Fast Track Designation for treatment of AML patients unfit for standard chemotherapy, and FDA and EMA Orphan Drug Designations, which entitle Biosight to seven and ten years of market exclusivity in the U.S. and Europe, respectively, upon aspacytarabine marketing approval for the treatment of AML in each territory.

Interim results from an ongoing Phase 2b study evaluating aspacytarabine as a single-agent first-line AML therapy demonstrate safety and single-agent activity, and additional studies are ongoing to evaluate aspacytarabine as a second line treatment for patients with relapsed or refractory MDS or AML. For more information regarding the Phase 2b clinical study of BST-236, please visit www.clinicaltrials.gov.