On April 7, 2021 Curaleaf Holdings, Inc. (CSE: CURA / OTCQX: CURLF) ("Curaleaf" or the "Company"), a leading international provider of consumer products in cannabis reported that it has successfully completed the acquisition of EMMAC Life Sciences Limited ("EMMAC"), the largest vertically integrated independent cannabis company in Europe, for base consideration of approximately US$50 million in cash and 17.5 million shares of Curaleaf, with additional consideration to be paid based upon the successful achievement of performance milestones (Press release, EMMAC Life Sciences, APR 7, 2021, View Source [SID1234577683]). Curaleaf has simultaneously established Curaleaf International Holdings Limited ("Curaleaf International") in Guernsey to hold the EMMAC investment and further its European expansion.

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To accelerate the expansion of Curaleaf International, Curaleaf has secured an investment of US$130 million from a single strategic institutional investor in exchange for 31.5% equity stake in Curaleaf International, implying a $413 million Post Money valuation, with US$80 million in cash available to spend. The subscription will fund the entire cash portion of the EMMAC acquisition consideration of US$50 million with the remaining US$80 million to be used to fund Curaleaf International’s current capital expenditures plan through 2022, as well as its pipeline of potential acquisitions. This infusion of outside capital into Curaleaf International significantly accelerates Curaleaf’s expansion plans in Europe by fully funding Curaleaf’s cash outlay for the EMMAC acquisition and providing the capital required to support Curaleaf International’s near-term European rollout. With its foreseeable expansion budget fully funded, Curaleaf’s new international business can focus on executing its further European expansion.

Curaleaf and the strategic investor have entered into a shareholders’ agreement regarding the governance of Curaleaf International pursuant to which Curaleaf will have control over operational issues as well as raising capital and the ability to exit the business. In addition, the strategic investor’s stake is subject to put/call rights which permits either party to cause the stake to be bought out by Curaleaf for Curaleaf equity starting in 2025.

Boris Jordan, Executive Chairman of Curaleaf, stated, "The successful completion of our acquisition of EMMAC, and the formation of our new Curaleaf International business, marks a transformational launching point for our entrance into the European cannabis market. Building on our market leading position in the U.S., this transaction establishes Curaleaf as the global, pure play, cannabis market leader by revenue and geographic reach. With our single strategic institutional investor, we have set a strong foundation for Curaleaf International’s future growth trajectory. On behalf of the Curaleaf Board of Directors and management team, we are thrilled to welcome Antonio Costanzo, co-founder and CEO of EMMAC, as the CEO of Curaleaf International, and the entire EMMAC team to Curaleaf."

The new Curaleaf International platform includes cultivation, EU GMP-certified processing, distribution, and R&D operations across several key European medical cannabis markets, including the United Kingdom, Germany, Italy, Spain and Portugal. Terra Verde, Curaleaf International’s European market cultivation facility in Portugal, is one of the oldest licensed cannabis growing facilities in Europe with approximately 2 hectares of cultivation area and is an industry leader on the cannabis production cost efficiency front. The Portugal based cultivation facility provides Curaleaf International with the potential to serve customers across key European medical cannabis markets as well as supporting exports to countries such as Israel, among others. Curaleaf International plans to significantly increase its cultivation capacity in 2021, and to exceed 10 tons per year by 2022, in order to accommodate future growth related to the expansion of access to cannabis across the major European medical and adult-use, as well as export markets. Curaleaf International also has an operational presence and partnerships in European Union countries that are enacting new medical cannabis access programs. Curaleaf International will also serve as the platform for other possible acquisitions in Europe and adjacent areas, and for its participation in pilot adult use programs.

Joseph Bayern, CEO of Curaleaf, commented, "As the consumer and political liberalization trends around cannabis that are sweeping the U.S. are increasingly taking hold across Europe, our expansion into the international cannabis market presents tremendous new long-term growth opportunities for Curaleaf. With the European population of nearly 748 million[1], the potential European addressable market is more than twice the size of the U.S. addressable market[2]. With the ability to operate our new European business across country borders, with one or two cultivation sites and one manufacturing center to serve the entire region in most cases, combined with our ability to leverage the strength of our consumer packaged goods strategies and innovations from our U.S. operations, we see enormously positive implications for our ability to quickly and efficiently scale the business across Europe."

Following the successful completion of the transaction, Mr. Antonio Costanzo has been appointed as the new Chief Executive Officer of Curaleaf International, with the former EMMAC management team continuing to lead Curaleaf’s new European presence as well as driving local European strategy and day-to-day operations.

Antonio Costanzo, CEO of Curaleaf International, commented, "This is an important day for the European cannabis market as EMMAC transitions to Curaleaf International. I look forward to working closely with the Curaleaf team to shape the future of cannabis for our patients and customers around the world. We will retain our science-led approach to continue to deliver best in class cannabis products for Europe’s growing medical cannabis market, and will work closely to leverage the consumer packaged goods experience and innovation from the U.S. to capitalize on the emerging adult-use market as legislation allows. We are now very well positioned to realize our aggressive growth ambitions."

On April 7, 2021 Daiichi Sankyo Company, Limited (hereafter Daiichi Sankyo) reported the first patient has been dosed in the first-in-human phase 1/2 study of DS-1594, a selective small-molecule menin inhibitor, in adults with relapsed/refractory acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) (Press release, Daiichi Sankyo, APR 7, 2021, https://www.businesswire.com/news/home/20210407005234/en/Phase-12-Trial-Initiated-for-Daiichi-Sankyo%E2%80%99s-Menin-Inhibitor-DS-1594-in-Patients-with-Acute-Myeloid-Leukemia-and-Acute-Lymphoblastic-Leukemia [SID1234577699]). The trial is being conducted by The University of Texas MD Anderson Cancer Center under an existing strategic research collaboration.

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Inhibition of the menin protein is being studied as a novel treatment approach for acute leukemias with MLL rearrangement (MLLr) or NPM1 mutation (NPM1m), two gene alterations that drive cancer development and growth.1 MLLr occurs in approximately 5 to 10% of acute leukemia patients and is associated with aggressive disease, reduced treatment response and poor prognosis.2 NPM1m occurs in about 30% of patients with AML.3 There are currently no medicines specifically approved for MLLr or NPM1m leukemias and no approved menin inhibitors.

"Research has shown that the menin protein, which binds to MLL, plays a critical role in the development and growth of leukemias with MLL rearrangement," said Arnaud Lesegretain, Vice President, Oncology R&D and Head, Alpha Portfolio, Daiichi Sankyo. "Our scientists designed DS-1594 to inhibit the menin-MLL interaction and disrupt the intracellular activity implicated in leukemogenesis. Together with MD Anderson, we will evaluate DS-1594 as a potential therapeutic option for patients with AML or ALL who have exhausted standard treatments."

The collaboration with MD Anderson is focused on accelerating development of Daiichi Sankyo pipeline therapies for AML, including phase 1 and 2 clinical trials to evaluate single and combination regimens, translational research to explore novel biomarkers, and pre-clinical studies aimed at identifying resistance mechanisms.

About the Study

MD Anderson will sponsor and lead an open-label, non-randomized, multi-arm phase 1/2 study to evaluate DS-1594 in single and combination regimens for patients with relapsed/refractory AML and ALL.

The primary objective of the phase 1 part of the study is to determine the maximum tolerated dose and recommended phase 2 dose of DS-1594 in up to 54 patients with AML or ALL regardless of mutation status. Primary endpoints include dose-limiting toxicities, recommended phase 2 dose and safety profile. Secondary endpoints include complete remission rate (CR) and CR with partial hematologic recovery rate (CRh).

In the phase 2 part of the study, DS-1594 will be further evaluated at the established dose in four expansion cohorts of patients with specific genetic markers. Patients with relapsed/refractory AML with MLLr or NPM1m will receive DS-1594 as monotherapy (Cohorts A and B) or in combination with azacitidine and venetoclax (Cohort C), and patients with ALL with MLLr will receive DS-1594 in combination with a mini-HCVD regimen (Cohort D). The primary endpoints are safety, CR/CRh rates for the AML cohorts, and CR/CR with incomplete hematologic recovery rates (CRi) for patients in the ALL cohort.

A number of secondary efficacy and pharmacokinetic endpoints along with exploratory pharmacodynamic and biomarker endpoints will also be evaluated. Up to 170 patients will be enrolled in the study, which will initially be conducted only at MD Anderson with global expansion planned for phase 2. For more information, visit Clinicaltrials.gov.

About Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia

More than 474,500 new cases of leukemia were reported globally in 2020 with more than 311,500 deaths.4 In the U.S., there were approximately 60,530 new cases of leukemia and 23,100 deaths in 2020.5

AML is the most common form of acute leukemia in adults, accounting for about 33% of all new cases.6 An aggressive and heterogenous cancer originating in bone marrow, AML is characterized by a five-year survival rate of 28.7%, the lowest by far among the major leukemia subtypes.7 Standard chemotherapy remains the main treatment option for most patients with AML with or without targeted therapy. Newer treatments for genetically defined AML subtypes have increased options and improved response rates and outcomes for some patients, but primary and secondary resistance remain a challenge and new types of therapies continue to be researched.8

ALL is a less common form of leukemia with 6,150 new cases estimated in the U.S. in 2020.9 The overall five-year survival rate for ALL is 68.8% among patients of all ages but significantly lower for adults.10 ALL is typically treated with standard chemotherapy-based regimens with or without targeted therapy.9

About MLL, NPM1 and Menin

The MLL (mixed-lineage leukemia) gene, also known as KMT2A, is important in sustaining hematopoietic stem cells and is known to undergo chromosomal translocations or epigenetic changes resulting in the expression of MLL fusion proteins that ultimately drive formation and growth of leukemia.11 Approximately 5 to 10% of acute leukemias harbor the MLL rearrangement, with a five-year overall survival rate of about 35%.11

The NPM1 (nucleophosmin 1) mutation causes aberrant expression of the NPM1 protein, which is involved in functions, including cell proliferation. NPM1m is observed in approximately 30% of AML patients with a five-year overall survival rate of about 50%.3

Menin is a scaffold protein that interacts with a multitude of other proteins to regulate gene expression and cell signaling.11 The interaction between menin and MLL proteins is critical to the leukemogenic activity in MLLr leukemia and is also reported to play a key role in development of NPM1m leukemia.1 Scientific evidence supports inhibition of the menin-MLL interaction as a therapeutic approach for acute leukemias.11 There are currently no medicines specifically approved for MLLr or NPM1m leukemias and no approved menin inhibitors.

About DS-1594

DS-1594 is a potent and selective small molecule menin inhibitor in clinical development in the Alpha portfolio of Daiichi Sankyo. DS-1594 was designed to target and disrupt the protein-protein interaction of menin and MLL to inhibit leukemic cell growth and proliferation. In preclinical studies, DS-1594 displayed selective growth inhibition against AML and ALL cells with MLLr and demonstrated robust and durable anti-tumor activity in AML models with an acceptable safety profile.12 DS-1594 is an investigational agent that has not been approved for any indication in any country. Safety and efficacy have not been established.

On April 7, 2021 ENTEROME SA, a clinical stage biopharmaceutical company developing novel drugs based on its unique ability to de-code molecular interactions in the gut microbiome impacting human health, reported that Pierre Belichard, CEO, will present an overview of the Company and take part in 1-on-1 meetings with institutional investors at the following conferences (Press release, Enterome, APR 7, 2021, View Source;utm_medium=rss&utm_campaign=enterome-to-present-at-upcoming-conferences [SID1234577684]):

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European Biotech Investor Days: April 7-8
Jefferies Microbiome-based therapeutics Summit: April 22
Jefferies Virtual Healthcare Conference: June 1-3
Enterome’s CBO, Anne Dagallier, will participate and take part in 1-on-1 meetings with potential business partners at the following conferences:

Digestive Disease Week (DDW): May 21-23
BIO International Convention: June 14-18

On April 7, 2021 Nucleix, a liquid biopsy company revolutionizing cancer treatment by detecting the disease earlier, reported that it has secured $55 million from a syndicate of leading life science investors in an oversubscribed financing round (Press release, Nucleix, APR 7, 2021, View Source [SID1234577700]).

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The round was led by RA Capital Management, with participation from new investors including funds and accounts managed by BlackRock, Lilly Asia Ventures, LYFE Capital and MILFAM. Existing investors participating in the round include OrbiMed, Aurum Ventures, DSC Investment, OCI Bio Investments and Zohar Zisapel. Nucleix will utilize the proceeds of the financing to continue the rapid advancement of its unique methylation technology, known as EpiCheck, and to develop Lung EpiCheck, its lead product for the early detection of lung cancer.

"Early detection of cancer from a blood sample is like listening for a whisper in a crowded room – you need to separate a faint signal from considerable background noise. EpiCheck minimizes sample loss and background noise while detecting minute cancer epigenetic signals with greater sensitivity than other technologies," said Chris Hibberd, chief executive officer of Nucleix. "This new funding enables us to further demonstrate the power of the technology through a focused program in lung cancer, advancing tests designed to be highly sensitive, easily deployed and cost effective."

EpiCheck is an ultra-sensitive technology for the detection of methylation changes and is compatible with both next-generation sequencing (NGS) and polymerase chain reaction (PCR) platforms. Nucleix is applying the NGS application of EpiCheck for deep discovery, to reveal new biomarkers that may be used in the early detection and monitoring of cancer. In turn, these discoveries can be advanced as highly sensitive tests using the PCR application of EpiCheck, with the potential to run cost-effectively in both centralized and local laboratories.

Lung EpiCheck is a highly sensitive, methylation-based blood assay for the early detection of lung cancer. The test analyzes subtle, disease-specific changes in DNA methylation markers meeting the needs of its target population – current and past smokers – to catch cancer earlier when treatment can be most effective. In October 2020, clinical data on the first generation of Lung EpiCheck was published in the European Respiratory Journal. Nucleix is now developing an improved version of the assay and will initiate a prospective study to validate the test, with the goal of making it available in 2022.

"The U.S. Preventive Services Task Force (USPSTF) recently updated the screening guidelines for high-risk lung cancer patients to double the number of people who qualify for annual screening1, but a challenge remains as less than 10% of those eligible in the United States follow the guidelines today," said Aharona Shuali, M.D., VP Medical. "Lung EpiCheck has the potential to provide an effective screening option that increases compliance and drives more patients to follow guidelines in the United States – increasing chances of patients having a long-term benefit."

About Lung EpiCheck

Lung EpiCheck is designed to provide a simple blood test that detects lung cancer at its earliest stages. The test utilizes NGS and PCR-based technology for highly sensitive analysis of subtle, disease-specific changes in DNA methylation markers. Lung EpiCheck is being developed for potential use in individuals with a history of smoking who are at high-risk of developing lung cancer, and do not comply with the guidelines for annual screening with low-dose computed tomography (LDCT) scans. The test is not yet commercially available.

On April 7, 2021 TriSalus Life Sciences reported that The American Association for Cancer Research (AACR) (Free AACR Whitepaper) will host its annual meeting, AACR (Free AACR Whitepaper) 2021, virtually, over two weeks: April 10-15 and May 20-26 (Press release, TriSalus Life Sciences, APR 7, 2021, View Source [SID1234577888]). The meeting program covers the latest discoveries across the spectrum of cancer research and highlights the work of the best minds in research and medicine from institutions all over the world.

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