On July 14, 2021 Nkarta, Inc. (Nasdaq: NKTX), a biopharmaceutical company developing engineered natural killer (NK) cell therapies to treat cancer, reported that it has signed a lease agreement for a facility to support research and development and future commercial manufacturing of Nkarta’s cell therapy pipeline (Press release, Nkarta, JUL 14, 2021, View Source [SID1234584866]). The new facility will also serve as the company’s headquarters with office space and research facilities. The manufacturing center will be custom designed to complement Nkarta’s state-of-the-art technology platform and optimize the production of its multiple off-the-shelf NK cell therapy investigational products. Nkarta plans to produce materials for potential pivotal clinical trials and commercial launch at the new center.

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"Our goal is to ensure that cost-effective, commercial-scale production of cell therapies can be made available widely and rapidly to the cancer patients who need them, and we expect this new facility will enable us to do just that," said Paul J. Hastings, President and CEO of Nkarta. "As we advance our NKX101 and NKX019 clinical programs and enhance our proprietary platform with exciting new capabilities like CRISPR Cas9 genome engineering, we believe our expanded footprint will drive continued operational excellence and accelerate the development of transformative NK cell therapies for a broad range of cancers."

Earlier this year, Nkarta completed the construction and qualification of a 2,700 square foot cGMP facility at its primary location in South San Francisco, California. This current clinical manufacturing facility was designed to integrate with Nkarta’s internal process development expertise and meet the production needs of Nkarta’s research activities and early stage clinical trials. Nkarta is currently manufacturing clinical supply for its planned Phase 1 study of NKX019, expected to start in the second half of 2021, and plans to transfer the production of NKX101 and other proprietary platform materials to the clinical manufacturing facility in the future.

The newly leased facility in South San Francisco will be built-out as a multi-product facility and is expected to be operational by the end of 2023. At full capacity, the manufacturing center is expected to have the flexibility to produce commercial supply of multiple cell therapy products. Nkarta will also consolidate administrative offices and research and development laboratories at the new site.

About NKX101
NKX101 is an investigational, off-the-shelf cancer immunotherapy that uses natural killer (NK) cells derived from the peripheral blood of healthy donors and engineered with membrane-bound IL15 and a chimeric antigen receptor (CAR) targeting NKG2D ligands on tumor cells. NKG2D, a key activating receptor found on naturally occurring NK cells, induces a cell-killing immune response through the detection of stress ligands that are widely expressed on cancer cells. By engineering NKX101 with the proprietary NKG2D-based CAR, the ability of NK cells to recognize and kill tumor cells in pre-clinical models is increased significantly compared to non-engineered NK cells. The addition of membrane-bound IL15, a proprietary version of a cytokine for activating NK cell growth, has been shown in pre-clinical models to enhance the proliferation, persistence and sustained activity of NK cells. A multi-center Phase 1 clinical trial of NKX101 in patients with relapsed/refractory acute myeloid leukemia (AML) or higher risk myelodysplastic syndromes (MDS) is currently enrolling. Additional information about the clinical trial is available on ClinicalTrials.gov, identifier NCT04623944.

About NKX019
NKX019 is an investigational, off-the-shelf cancer immunotherapy that uses natural killer (NK) cells derived from the peripheral blood of healthy donors and engineered with a CD19-directed chimeric antigen receptor (CAR) and a proprietary, membrane-bound form of interleukin 15 (IL-15). CD19 is a biomarker for normal and malignant B cells, and it is a validated target for B cell cancer therapies. Via its CAR, NKX019 targets and binds to CD19 and eliminates CD19-expressing cells via a robust immune response in preclinical studies. Preclinical models also demonstrate enhanced proliferation, persistence and activity of NK cells with the membrane-bound IL-15, an important cytokine for NK cell survival. Initiation of a Phase 1 clinical trial of NKX019 in patients with relapsed/refractory B cell malignancies in multiple centers in the United States and Australia is planned for the second half of 2021.

About Nkarta’s Platform and Natural Starting Materials
Nkarta’s engineering platform utilizes healthy adult donors as the source for NK cells. By enlisting this natural source of NK cells, Nkarta starts with bona fide NK cells endowed with inherent tumor-recognizing ability and potent cytotoxic function. Healthy donor-derived NK cells are also available in abundance, providing a large quantity of cells with which to begin the efficient two-week manufacturing process. Finally, healthy donor-derived adult cells consist of a diverse repertoire of NK cells, providing Nkarta with the potential to capitalize on the inherent diversity of the innate immune system in selecting donors or NK cell populations with optimal characteristics.

About Nkarta’s NK Cell Technologies
Nkarta has pioneered a novel discovery and development platform for the engineering and efficient production of allogeneic, off-the-shelf natural killer (NK) cell therapy candidates. The approach harnesses the innate ability of NK cells to recognize and kill tumor cells. To enhance the inherent biological activity of NK cells, Nkarta genetically engineers the cells with a targeting receptor designed to recognize and bind to specific proteins on the surface of cancerous cells. This receptor is fused to co-stimulatory and signaling domains to amplify cell signaling and NK cell cytotoxicity. Upon binding the target, NK cells become activated and release cytokines that enhance the immune response and cytotoxic granules that lead to killing of the target cell. All of Nkarta’s NK current cell therapy candidates are also engineered with a membrane-bound IL15, a proprietary version of a cytokine known for activating NK cell growth, to enhance the persistence and activity of the NK cells.

Nkarta’s manufacturing process generates an abundant supply of NK cells that, at commercial scale, is expected to be significantly lower in cost than other current allogeneic and autologous cell therapies. Key to this efficiency is the rapid expansion of donor-derived NK cells using a proprietary NKSTIM cell line, leading to the production of hundreds of individual doses from a single manufacturing run. The platform also features the ability to freeze and store CAR NK cells for an extended period of time and is designed to enable immediate, off-the-shelf administration to patients at the point of care.

On July 14, 2021 PharmaCyte Biotech, Inc. (OTCQB: PMCBD), a biotechnology company focused on developing cellular therapies for cancer and diabetes using its signature live-cell encapsulation technology, Cell-in-a-Box, reported that the production and shipping of test materials and study plan designs for the biocompatibility studies requested by the U.S. Food and Drug Administration (FDA) have been completed (Press release, PharmaCyte Biotech, JUL 14, 2021, View Source [SID1234584883]).

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The "CypCaps" product represents a refinement of the original encapsulated cells that were successfully tested in previous clinical trials. In order to show comparability, the FDA requested that standard biocompatibility studies be performed by a Contract Research Organization (CRO) in accordance with regulatory requirements. Study plans have been finalized and the Company’s most time-consuming study has already commenced and is ongoing. These studies required the production of additional capsule material for testing, and this effort has been completed by Austrianova. Some of the material also had to be prepared and treated in accordance with the requirements of the tests. This work has also been completed and the materials, both treated and non-treated, have been shipped to and received by, the CRO.

PharmaCyte’s Chief Executive Officer, Kenneth L. Waggoner, said, "The commencement of the most rate-limiting study represents yet another major step for complying with the FDA’s requirements. As our work continues to advance to produce the required data to satisfy the FDA and move toward an open IND, our expectation is to complete the FDA’s list of requirements in the Fourth Quarter of this year.

"Additionally, as we continue our work to achieve an open IND, we have also continued our plan to make ourselves more attractive to the investment community and uplist to Nasdaq. We believe the reverse stock split, which was recently enacted, will assist the Company in pursuing additional financing activities and other strategic transactions to support the development of our product candidates. We believe this is a necessary step before the Company’s common stock can be listed on a national stock exchange like Nasdaq, which is our expectation. Nasdaq is requiring the Company to trade above $4.00 for 10 trading days before we can uplist."

On July 13, 2021 Sanofi’s ongoing efforts to simplify its Consumer Healthcare portfolio and accelerate its growth trajectory, reported that the company has signed an agreement with HYPERA S.A. ("Hypera Pharma") for the divestiture of eight products commercialized in Latin America (Press release, Sanofi, JUL 13, 2021, View Source [SID1234584867]). The agreement also includes four prescription products from the General Medicine portfolio.

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"As discussed during our Capital Markets Day in February, simplifying the CHC product portfolio is an important part of our strategy to focus our resources and efforts where we can bring the most value, especially to consumers. We are pleased these products will continue to be available for consumers as we focus on becoming a fully integrated standalone business" said Julie Van Ongevalle, Executive Vice-President, Sanofi and Head of Sanofi Consumer Healthcare.

Sanofi does not anticipate any impact of this divestiture to its Latin American-based workforce.

The transaction is expected to close at the end of 2021, subject to approval of relevant regulatory authorities and other customary closing conditions.

On July 13, 2021 Cyclacel Pharmaceuticals, Inc. (NASDAQ: CYCC, NASDAQ: CYCCP; "Cyclacel" or the "Company"), a biopharmaceutical company developing innovative medicines based on cancer cell biology, reported that dosing of the first patient in the Company’s multi-cohort Phase 1/2 study of oral fadraciclib in patients with advanced solid tumors (Press release, Cyclacel, JUL 13, 2021, View Source [SID1234584817]).

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"Advancing oral fadraciclib, our lead candidate, into this Phase 1/2 trial, represents a key clinical milestone and corporate objective for our team," said Spiro Rombotis, Cyclacel’s President and Chief Executive Officer. "This is the first of four streamlined Phase 1/2 studies we plan to open over the coming months as we expand our clinical programs to evaluate the potential of fadraciclib and CYC140, our oral PLK1 inhibitor, first in solid tumors and lymphomas and then in leukemias. We look forward to providing periodic updates on our clinical progress and data from these open-label studies."

"We are pleased to have dosed the first patient in this study and are delighted by the enthusiasm and strong interest from current and prospective investigators," said Mark Kirschbaum M.D., Senior Vice President & Chief Medical Officer of Cyclacel. "The study has initially opened at City of Hope and MD Anderson Cancer Center with more sites to join later on. We are building an excellent network of participating institutions both in terms of clinical and scientific expertise. In previous studies with single agent, intravenous fadraciclib we have observed durable suppression of MCL1 and other mechanistically-related proteins, including cyclin E and MYC, at tolerated doses. In addition, a patient with MCL1 amplified, advanced endometrial cancer experienced deep PR and 100% shrinkage of her target tumor lesions on single agent fadraciclib treatment. We are excited to begin mid-stage development of fadraciclib with the objective of registration-enabling outcomes and offering a new treatment option for patients with advanced solid tumors or lymphomas."

"Based upon prior clinical activity shown to date, further exploration of this novel CDK2/9 inhibitor is warranted across a number of solid tumor histologies," said Miguel Villalona-Calero, M.D., co-leader of the Developmental Cancer Therapeutics Program and Professor, Department of Medical Oncology & Therapeutics Research at the City of Hope, a world-renowned, independent research and treatment center for cancer, diabetes and other life-threatening diseases. "We look forward to enrolling patients in this trial and evaluating the potential treatment benefit of this experimental therapy both as a single agent and in combinations."

The Phase 1/2 registration-directed trial (CYC065-101) uses a streamlined design and will first determine the recommended Phase 2 dose (RP2D) for single-agent, oral fadraciclib. Once RP2D has been established, the trial will immediately enter into proof-of-concept, cohort stage, using a Simon 2-stage design, where single agent fadraciclib will be administered to patients in up to eight cohorts defined by histology thought to be sensitive to the drug’s mechanism of action and informed by the clinical activity of fadraciclib in previous studies. The cohorts will include patients with breast cancer (selected for metastatic, hormone receptor positive, HER-2 negative, post-CDK4/6 inhibitor; HER-2 refractory; or triple negative), colorectal (including KRAS mutant), endometrial, hepatocellular and ovarian cancers, as well as certain lymphomas. An additional basket cohort will enroll patients with biomarkers relevant to the drug’s mechanism, including MCL1, MYC and cyclin E, regardless of histology. The protocol allows for expansion of a cohort based on response which may allow acceleration of the clinical development and registration plan for fadraciclib.

About Cyclin-Dependent Kinases and Fadraciclib

Cyclin-dependent kinases (CDKs) are critical for cell cycle control and transcriptional regulation. Dysregulated CDKs have been linked to the cancer hallmarks of uncontrolled proliferation and increased cancer cell survival. Fadraciclib, a next generation CDK inhibitor, is a highly selective, potent, orally and intravenously available, inhibitor of CDK2 and CDK9. CDK2 drives cell cycle transitions and CDK9 regulates transcription of genes through phosphorylation of the carboxy-terminal domain (CTD) of RNA polymerase II (RNAP II). By inhibiting CDK2 and CDK9 fadraciclib causes apoptotic death of cancer cells at sub-micromolar concentrations.

Preclinical data suggest that fadraciclib may benefit patients with certain cyclin E-addicted or MYC-amplified solid tumors, including certain forms of breast cancer, neuroblastoma, ovarian cancer, uterine serous carcinoma and adult and pediatric hematological malignancies, such as ALL, AML, B-cell lymphoma, CLL, and multiple myeloma. Similarly to FDA-approved CDK4/6 inhibitors, fadraciclib may be useful in combination with other anticancer drugs, including HER2 inhibitors, such as trastuzumab, or BCL2 inhibitors, such as venetoclax.

In a prior Phase 1 open-label trial (CYC065-01), patients with high copy CCNE (cyclin E), MYC or MCL1 showed sensitivity to intravenously-administered, single-agent fadraciclib. A heavily pretreated patient with MCL1 amplified endometrial cancer achieved a radiographically confirmed partial response (PR) after a month and a half on fadraciclib. This patient continues on therapy for almost two years and reduction in her target tumor lesions has reached 100%. An additional patient with cyclin E amplified ovarian cancer achieved stable disease with 29% shrinkage in her target tumor lesions.

On July 13, 2021 ISA reported the closing of a EUR 26 million funding round with participation from new investors including Invest-NL and existing investors including Regeneron (Press release, ISA Pharmaceuticals, JUL 13, 2021, View Source [SID1234584799]). The proceeds of this round will be used to advance the lead product ISA101b towards first marketing authorization as well as to broaden the clinical pipeline of immunotherapies based on the Synthetic Long Peptide (SLP) platform technology.

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Gerben Moolhuizen, CEO of ISA Pharmaceuticals, said, "We are very happy with the continued support of our existing partners and shareholders. Invest-NL’s support underlines the innovation at ISA Pharma and potential impact of our SLP immunotherapies for the treatment of serious diseases."

SLP immunotherapies act through the specific activation of the patient’s own immune system. Lead product ISA101b targets cancers caused by human papilloma virus type 16 (HPV16). It is in late stage clinical development in three trials for the treatment of advanced stages of HPV16-positive head and neck cancer and cervical cancer in combination with Libtayo (cemiplimab, anti-PD1 immunotherapy), which is being co-developed by Regeneron and Sanofi.

Leo Holwerda, Director Capital at Invest-NL, notes: "Our investment in ISA Pharmaceuticals is a good example of how our TOPSS program can help promising Dutch start-ups and innovative companies which were affected by COVID-19. Invest-NL is happy to support ISA Pharmaceuticals to accelerate its clinical studies and we are confident that the company will succeed in bringing its lead therapy for patients with HPV16-positive head & neck cancer and cervical cancer to the market. This innovative and impactful therapy will strengthen the prospects of many patients."

Persistent HPV16 infection can cause head & neck, cervical and anogenital cancers. These cancers can be severe and life-threatening with low overall survival rates once these cancers progress to advanced stages. HPV16 is a major cause of head & neck cancer with over 25,000 new cases and 11,000 deaths in Europe (source) and 46,000 new cases and 9,000 deaths in the US (source).
HPV16 is also responsible for about 50% of cervical cancer cases. Cervical cancer is the 2nd most common cancer in women aged 15 to 44 years in Europe, with over 60,000 new diagnoses and 25,000 deaths each year in Europe. Globally there are more than 500,000 new patients and 300,000 deaths (source).

The SLP technology platform is at the basis of several ISA pipeline products that are scheduled to proceed into clinical trials over the next few years. Three promising products are in the final stages of pre-clinical development. ISA104 targets the hepatitis B virus (HBV) in chronically infected patients. Chronic HBV is a major cause of liver cirrhosis and liver cancer and affects over 250 million people worldwide (source). ISA103 is aimed at tumours that express PRAME, a protein closely associated with the malignant behaviour of cells in numerous types of cancers. ISA106 is a potential treatment for high risk COVID-19 infected patients.