On June 30, 2022 Cellectis (the "Company") (Euronext Growth: ALCLS – NASDAQ: CLLS), a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies, reported that research data on its novel immune-evasive universal CAR T-cells in Nature Communications, following an oral presentation at the American Society of Cell and Gene Therapy (ASGCT) (Free ASGCT Whitepaper) on May 16 (Press release, Cellectis, JUN 30, 2022, View Source [SID1234616406]).

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Cellectis’ next generation of universal CAR T-cells have the potential to improve the persistence and to allow large-scale deployment of T-cell product candidates in allogeneic settings against multiple malignancies.

Universal CAR T-cell therapies are poised to revolutionize the treatment of selected hematologic malignancies. However, realizing the full potential of CAR T in an allogeneic setting requires universal CAR T-cells that can kill target tumor cells, avoid depletion by the host immune system via the host versus graft reaction (HvG), and proliferate without attacking host tissues via the graft versus host reaction (GvH).

While the prevention of GvH can be readily addressed by the inactivation of T cell receptor T αβ (TCRαβ) expression in a CAR T-cell, prevention of HvG remains a major challenge.

To address this challenge, the Cellectis investigators engineered CAR T-cells to be deficient in Class 1 major histocompatibility complex (MHC-1) and to express the Natural Killer (NK) inhibitor HLA-E, in order to endow them with immune-evasive properties toward alloreactive Tc ells and NK cells.

"This engineering approach is very promising and could enable the universal CAR T-cells to become transiently invisible to NK and alloreactive T-cells, allowing them to eradicate tumor cells before being rejected by the patient’s immune system. This could enable the broad use of universal CAR T-cells in allogeneic settings, for the benefit of a wider population of patients." said Julien Valton, Ph.D., Vice President Gene Therapy at Cellectis.

"One potential advantage of this approach is to spare endogenous immune effectors and allow them to work in concert with CAR T-cells in the fight against hard-to-treat cancers, including solid tumors" said Laurent Poirot, Ph.D. Senior Vice President Immuno-Oncology at Cellectis.

The research data show that:

· Endowing universal CAR T-cells with immune-evasive properties via TALEN-mediated gene editing and adeno-associated virus (AAV)-dependent gene insertion, is highly efficient and specific, transferable to different CAR constructs and adaptable to conventional CAR T-cell manufacturing processes.

· Immune-evasive universal CAR T-cells overcame alloresponsive T-cell and NK cells attacks and exhibit prolonged antitumor activity, even in the presence of highly active NK cells.

· Immune-evasive properties against NK cells from most healthy donors and acute myeloid leukemia (AML) patients were similar, demonstrating the robustness and transportability of this hypoimmunogenic approach to persistence and warranting further evaluation in preclinical and clinical settings

On June 30, 2022 Nanostics Inc., a precision health diagnostics company, reported that positive data from a pre-biopsy clinical validation study of its ClarityDX Prostate test designed to improve the accuracy of detecting clinically significant prostate cancer in men that are at risk of the disease (Press release, Nanostics, JUN 30, 2022, View Source [SID1234616423]).

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The ClarityDX Prostate test uses a proprietary machine-learning algorithm that combines data from two biological biomarkers and three clinical biomarkers to generate a risk score for clinically significant prostate cancer. The ClarityDX Prostate test is intended to be used as a reflex test for men with elevated levels of PSA, the current prostate cancer screening test, and is designed to help physicians and patients make a more informed decision to proceed with biopsy or not.

"We are extremely excited to announce positive results from the clinical validation study of the ClarityDX Prostate test in Alberta", John Lewis, CEO of Nanostics said, "Implementing ClarityDX Prostate as a reflex test for men with elevated PSA levels will improve decision-making for men and their families, while providing substantial savings for healthcare systems and resulting in better health outcomes for men with prostate cancer."

A total of 1,437 men between 40-75 years of age, with elevated PSA levels, no prior prostate cancer diagnosis, and who were referred for prostate biopsy, were recruited for this clinical study. Algorithmic risk models to predict prostate cancer or clinically significant (grade group ≥2) prostate cancer were generated using data from 1036 men recruited at the Kipnes Urology Center in Edmonton, AB, and a site in Baltimore, USA. These models were then tested in a validation cohort of 401 men recruited at the Prostate Cancer Center in Calgary, AB.

The ClarityDX Prostate test provided 94% sensitivity, 37% specificity, 49% positive predictive value, and 90% negative predictive value for predicting clinically significant (grade group ≥2) prostate cancer. The potential impact of the ClarityDX Prostate test is considerable; implementation could eliminate up to 37% of unnecessary biopsies and significantly reduce the number of unnecessary treatments for prostate cancer. The results from the study are being submitted for peer-reviewed publication. Beyond the immediate cost savings to the healthcare system, the launch of the ClarityDX Prostate test will positively impact the overall healthcare experience and quality of life for men with prostate cancer.

The study was conducted in partnership with DynaLIFE Medical Labs and the Alberta Prostate Cancer Research Initiative (APCaRI) at the University of Alberta. Funding for the clinical study comes in part from The Bird Dogs, Motorcycle Ride for Dad, Alberta Cancer Foundation, Alberta Innovates, the University Hospital Foundation Kaye Fund, and the Frank and Carla Sojonky Chair in Prostate Cancer Research funded by the Alberta Cancer Foundation, held by Dr. John Lewis from 2012 to 2022.

On June 30, 2022 (the "Effective Date"), Geron Corporation (the "Company") reported that it entered into a second amendment (the "second amendment") to the Loan and Security Agreement dated September 30, 2020, as amended (the "Loan Agreement") with Hercules Capital, Inc., as administrative agent and collateral agent (in such capacity, the "Agent") and a lender, and Silicon Valley Bank, as a lender (collectively with Hercules Capital, Inc., the "Lenders") (Filing, 8-K, Geron, JUN 30, 2022, View Source [SID1234616426]). Under the second amendment, the aggregate principal amount available to the Company increased from $75 million to $125 million (the "Term Loan"), with such principal being available in a series of tranches, subject to certain terms and conditions. As of June 30, 2022, the total outstanding principal amount under the Loan Agreement is $50 million.

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The tranches for the remaining $75 million of the Term Loan (the "Remaining Tranches") available to the Company are as follows: a) the first remaining tranche of $20 million (the "First Tranche") is available within 30 days of the achievement of certain clinical and financial milestones until September 15, 2023, subject to the achievement of such milestones; b) the second remaining tranche of $10 million is available from January 1, 2023 until December 15, 2023, subject to the achievement of certain clinical and regulatory milestones, and satisfaction of certain other requirements; c) the third remaining tranche of $20 million is available from September 15, 2023 until September 15, 2024, subject to the achievement of certain clinical and regulatory milestones, and satisfaction of certain capitalization requirements; and d) the final tranche of $25 million is available through December 31, 2024, subject to the Lenders’ approval. With the exception of the final tranche, and subject to achievement of the applicable milestones and other requirements with respect to each tranche, utilization of the Remaining Tranches under the Term Loan is at the Company’s election.

Under the second amendment, the Company is required to pay 1.0% facility charge for each of the remaining tranches that is drawn down by the Company after the Effective Date, including 0.5% of facility charge with respect to the First Tranche paid at the Effective Date. If the Company chooses to prepay the principal with respect to any Remaining Tranche drawn down after the Effective Date, any such prepayment within the first 36 months after the Effective Date will be subject to a prepayment charge equal to 1.5% of the principal amount prepaid. No prepayment charge will be assessed for any prepayment occurring more than 36 months after the Effective Date.

The maturity date, interest only payment dates, end of term charges, collateral, events of default, representations, warranties and covenants remain consistent with the terms of the original Loan Agreement, except as follows:

●Beginning June 1, 2022 and prior to the potential achievement by the Company of regulatory approval for imetelstat (the "potential Regulatory Approval"), if any, the Company is required to maintain a minimum cash balance in an amount equal to the greater of: 50% of the outstanding principal amount under the Loan Agreement or $30 million.

●After the potential Regulatory Approval, if any, the minimum cash requirement may be satisfied through one of the following three options, as elected by the Company: a) maintaining a cash balance in an amount not less than 40% of the outstanding principal amount under the Loan Agreement; b) maintaining a cash balance in an amount not less than 25% of the outstanding principal amount under the Loan Agreement, if the Company’s market cap is or exceeds $750 million; or c) maintaining six month net product revenues of at least 70% of net product revenues forecasted by the Company, should any potential Regulatory Approval for imetelstat be obtained.

The descriptions of the second amendment to the Loan Agreement contained herein do not purport to be complete and are qualified in their entirety by reference to the complete text of the second amendment to the Loan Agreement, a copy of which will be filed as an exhibit to the Company’s Quarterly Report on Form 10-Q for the quarter ending June 30, 2022.

On June 30, 2022 Genmab A/S (Nasdaq: GMAB) reported its intent to submit a biologics license application (BLA) to the U.S. Food and Drug Administration (FDA) for subcutaneous epcoritamab (DuoBody-CD3xCD20), an investigational bispecific antibody, for the treatment of patients with relapsed/refractory large B-cell lymphoma (LBCL), in the second half of 2022 (Press release, Genmab, JUN 30, 2022, View Source [SID1234616408]).

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The BLA submission is supported by results from the large b-cell lymphoma (LBCL) cohort of the pivotal EPCORE NHL-1 open-label, multi-center trial evaluating the safety and preliminary efficacy of epcoritamab in patients with relapsed, progressive or refractory CD20+ mature B-cell non-Hodgkin lymphoma (B-NHL). In April 2022, Genmab and AbbVie announced the topline results from EPCORE NHL-1 trial. In June 2022, primary results were presented in a late-breaking oral presentation as part of the Presidential Symposium at the 27th Annual Meeting of the European Hematology Association (EHA) (Free EHA Whitepaper) (EHA2022) in Vienna, Austria.

"Relapsed or refractory large B-cell lymphoma is often difficult to treat, and patients are in need of novel therapies that are effective, tolerable and accessible," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab. "The results from the EPCORE NHL-1 trial, and other clinical trials evaluating epcoritamab in a variety of patients and treatment settings, have demonstrated that epcoritamab has the potential to offer people living with LBCL a new therapeutic advance with a manageable safety profile."

Epcoritamab is being co-developed by Genmab and AbbVie as part of the companies’ oncology collaboration. The companies are committed to evaluating epcoritamab as a monotherapy, and in combination, across lines of therapy in a range of hematologic malignancies, including an ongoing phase 3, open-label, randomized trial evaluating epcoritamab as a monotherapy in patients with relapsed/refractory DLBCL (NCT: 04628494).

About Large B-cell Lymphoma (LBCL)
LBCL is a fast-growing type of non-Hodgkin’s lymphoma (NHL), a cancer that develops in the lymphatic system and affects B-cell lymphocytes, a type of white blood cell. There are an estimated 150,000 new LBCL cases each year globally. LBCL includes DLBCL, which is the most common type of NHL worldwide and accounts for approximately 31 percent of all NHL cases.i,ii,iii,iv

About the EPCORE NHL-1 Trial
EPCORE NHL-1 is an open-label, multi-center safety and preliminary efficacy trial of epcoritamab including a phase 1 first-in-human, dose escalation part; a phase 2 expansion part; and an optimization part. The trial was designed to evaluate subcutaneous epcoritamab in patients with relapsed, progressive or refractory CD20+ mature B-NHL, including LBCL and DLBCL. Data from the dose escalation part of the study, which determined the recommended phase 2 dose, were published in The Lancet in 2021. In the phase 2 expansion part, additional patients are treated with epcoritamab to further explore the safety and efficacy of epcoritamab in patients with different types of relapsed/refractory B-NHLs who had limited therapeutic options.

The primary endpoint of the phase 2 expansion part was overall response rate (ORR) as assessed by an IRC. Secondary efficacy endpoints included duration of response, complete response rate, progression-free survival, overall survival, time to response, time to next therapy, and rate of minimal residual disease negativity.

About Epcoritamab
Epcoritamab is an investigational IgG1-bispecific antibody created using Genmab’s proprietary DuoBody technology. Genmab’s DuoBody-CD3 technology is designed to direct cytotoxic T cells selectively to elicit an immune response towards target cell types. Epcoritamab is designed to simultaneously bind to CD3 on T cells and CD20 on B-cells and induces T cell mediated killing of CD20+ cells.v CD20 is expressed on B-cells and a clinically validated therapeutic target in many B-cell malignancies, including diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma and chronic lymphocytic leukemia.vi,vii

On June 30, 2022 Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas" ), Nitto Denko Corporation (TSE: 6988, President: Hideo Takasaki, "Nitto"), and M. Heart Co., Ltd. (President and CEO: Yoshimi Mizunuma, "M. Heart") reported that the three companies have entered into an agreement for a sales pilot of disposable Holter ECG device "EG HolterTM" for the Japan market (Press release, Astellas, JUN 30, 2022, View Source [SID1234616392]). Based on this agreement, Astellas has established an e-commerce site for healthcare professionals and will start the sales pilot of the device today.

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This is Astellas’ first initiative in Rx+ program to promote a product through an e-commerce site. After verifying the business model through the sales pilot, Astellas will move to full-scale marketing of the product.

EG Holter is a holter electrocardiograph designed and developed by Nitto. Because it is a disposable device, it is hygienic and does not require maintenance. It is 6 mm thick,11 g in weight, has no cords, and is water resistance (IPX4). It is easy to attach and remove.

Data obtained by EG Holter will be analyzed by "MYHOLTER II", which is software for the holter analyzer jointly developed by Astellas and M. Heart. MYHOLTER II is a program that analyzes holter ECG data with a proprietary analytical algorithm using artificial intelligence (AI). M. Heart has obtained cerification for EG Holter and MYHOLTER II as medical device (Class II).

Astellas, Nitto and M. Heart have come together to create a simple, convenient, patient-centered solution for patients and medical institutions.

Medical costs for heart diseases and other cardiovascular diseases in Japan exceed 6 trillion yen per year―the highest of any disease category1. Of particular concern is cardiogenic cerebral embolism, which occurs when a thrombus that formed in the heart blocks an artery in the brain or neck. This has a high mortality rate (20%) and often results in severe sequelae, such as a bedridden state (40%)2. Atrial fibrillation is said to be the cause of cardiogenic cerebral embolism in 3 out of 4 cases2. Early detection of atrial fibrillation is an important social issue.

By providing a total solution that involves combining convenient ECG testing using the EG Holter and the data analysis using MYHOLTER II, Astellas, Nitto, and M. Heart propose to enable early detection and appropriate treatment of atrial fibrillation, a condition estimated to affect approximately 700,000 patients in Japan2, and contribute to the prolongation of healthy life expectancy.