On December 13, 2021 Samsung Biologics (207940.KS), the world’s leading contract development and manufacturing organization, reported that continues its strategic biopharmaceutical manufacturing collaboration with AstraZeneca (LSE/STO/Nasdaq: AZN) (Press release, Samsung BioLogics, DEC 13, 2021, View Source [SID1234596983]). The partnership is based on an expanded deal this year in May 2021 which followed the signing of a long-term strategic agreement made in September 2020. Under the agreement, valued at approximately $380 million up from the initial $331 million for the production of drug substance and drug product, Samsung Biologics manufactures AstraZeneca’s COVID-19 long-acting antibody (LAAB) combination, AZD7442, and will start to manufacture a cancer immunotherapy product from next year.

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Samsung Biologics and AstraZeneca expand strategic manufacturing partnership to include COVID-19 and cancer therapies
Samsung Biologics and AstraZeneca expand strategic manufacturing partnership to include COVID-19 and cancer therapies
AZD7442 is a combination of two LAABs being developed for the prevention and treatment of COVID-19. AZD7442 is the first LAAB to receive an EUA from the US Food and Drug Administration (FDA) for COVID-19 prevention and it has received authorizations from the US, France, Italy, and Bahrain.

AZD7442 has the potential to complement national vaccination programs by providing additional protection for those considered at increased risk of an inadequate response to a COVID-19 vaccine, including people who are immunocompromised, patients on dialysis, oncology patients, those taking medications after an organ transplant or those who are taking immunosuppressive drugs for conditions including multiple sclerosis and rheumatoid arthritis.

Pam Cheng, Executive Vice President, Global Operations and IT, AstraZeneca said, "Over the past year Samsung Biologics has been a highly capable and collaborative partner on our novel COVID-19 long-acting antibody combination. We are excited about expanding our work together into cancer immunotherapy and about laying the foundation for continued growth of our collaboration in the years ahead."

"We are delighted to continue expanding our strategic collaboration with AstraZeneca, a valuable partner we have witnessed first-hand to have a strong commitment to saving lives of patients," said John Rim, CEO of Samsung Biologics. "We will support our clients by bringing innovative solutions to an array of diseases, especially during this time when it is needed the most, and together find ways to expedite the delivery of crucial therapies to the market."

Samsung Biologics has been proactive in accommodating the varying needs of clients including the building of an additional facility, Plant 4, upon completion of which will allow the company to hold the world’s largest biomanufacturing capacity of 620,000L, and the addition of a messenger RNA vaccine drug substance (DS) manufacturing suite to the current facility in Songdo, ready for cGMP operations within the earlier part of the year in 2022.

On December 13, 2021 Celularity Inc. (Nasdaq: CELU) ("Celularity") reported that preclinical data on the development of its placental-derived allogeneic genetically modified NK cell therapy program (CYNK-101) and its placenta-derived allogeneic CAR-NK cell therapy program (CAR19-CYNK), respectively (Press release, Celularity, DEC 13, 2021, View Source [SID1234596914]). The Company reported its findings in two poster presentations at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Meeting and Exposition (ASH) (Free ASH Whitepaper) taking place in Atlanta and virtually December 11-14, 2021 .

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Poster no. 2773: "Human Placental CD34+-Derived Natural Killer Cells with High Affinity and Cleavage Resistant CD16 (CYNK-101) in Combination with Daratumumab for Immunotherapy Against CD38 Expressing Hematological Malignancies"

Session name: 703. Cellular Immunotherapies: Basic and Translational: Poster II
Presentation date/time: Sunday, 12 December 2021; 6:00 pm
Room: Georgia World Congress Center, Hall B5
Highlights: CYNK-101 is a cryopreserved, off the shelf, allogeneic NK cell product candidate, overexpressing a high IgG binding affinity, proteinase cleavage resistant, CD16 variant. The results show the synergistic effect of combining CYNK-101 with daratumumab to drive antibody dependent cellular cytotoxicity activity against CD38+ hematological malignancies in vitro and in vivo. In these studies, CYNK-101 was not susceptible to daratumumab-directed fratricide and did not display on-target, off-tumor cytotoxicity, suggesting CYNK-101 may be a unique NK cell platform that preserves innate immune function in the presence of daratumumab.

Poster no. 2779: "Development of CD19 CAR Engineered Human Placental CD34+-Derived Natural Killer Cells (CAR19-CYNK) As an Allogeneic Cancer Immunotherapy"

Session name: 703. Cellular Immunotherapies: Basic and Translational: Poster II
Presentation date/time: Sunday, 12 December 2021; 6:00pm
Room: Georgia World Congress Center, Hall B5
Highlights: The results demonstrate the feasibility and functionality of expressing a Chimeric Antigen Receptor (CAR) directed to CD19 on placental CD34+ derived, cryopreserved, off-the-shelf, allogeneic CYNK cells. The introduction of CAR in the product candidate CAR19-CYNK did not impact performance of CYNK cell manufacture and endowed additional tumor cell killing against resistant lymphoma cell lines in a CD19-dependent manner, when tested both in vitro and in vivo.

On December 13, 2021 Midatech Pharma PLC (AIM: MTPH; Nasdaq: MTP), a drug delivery technology company focused on improving the bio-delivery and biodistribution of medicines, reported that its Investigational New Drug (IND) application for a Phase 1 study of MTX110, a panobinostat complex to be administered by convection enhanced delivery in patients with recurrent glioblastoma multiforme (rGBM), has been cleared by the US FDA (Press release, Midatech Pharma, DEC 13, 2021, View Source [SID1234596931]). The 30-day review period has expired and the IND has been judged safe to proceed. Accordingly, Midatech has initiated preparations for a study start in the first half of 2022.

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Employing the Company’s MidaSolve technology, MTX110 solubilises panobinostat, a histone deacetylase (HDAC) inhibitor currently used in the treatment of multiple myeloma. In a liquid formulation as MTX110, panobinostat can be delivered directly to a patient’s tumour under constant pressure via a catheter system (Convection Enhanced Delivery, or "CED") thereby bypassing the blood-brain barrier and allowing for high drug concentrations and broader drug distribution in and around the tumour while simultaneously minimising systemic toxicity and other side effects. Panobinostat has demonstrated high potency against patient-derived tumour cells in in vitro and in vivo models.

GBM is the most common and aggressive form of brain cancer in adults, usually occurring in the white matter of the cerebrum. Treatments include radiation, surgical resection and chemotherapy although, in almost all cases, tumours recur. There are approximately 2-3/100,000(1) diagnoses of GBM per annum. Survival with standard of care treatment ranges from approximately 13 months in unmethylated MGMT patients to approximately 30 months in highly methylated MGMT patients(2). Glioblastoma is an intractable brain cancer.

The primary objective of the Phase I study will be to assess the safety and tolerability of MTX110 in patients with rGBM. The study is expected to include two clinical centres in the US and to begin recruiting H1 2022.

Dmitry Zamoryakhin, Chief Scientific Officer of Midatech, said:

"Our solubilising technology in combination with a CED system offers the potential to deliver significantly higher doses of panobinostat, a potent HDAC inhibitor, directly to the tumour. Importantly, this targeting approach is designed to limit systemic circulation of drug and therefore toxicity. This signal finding Phase I study could point the way to a new treatment paradigm for this intractable brain cancer."

This announcement contains inside information for the purposes of Article 7 of Regulation (EU) 596/2014 (MAR).

1.American Association of Neurosurgeons

2.Radke et al (2019). Predictive MGMT status in a homogeneous cohort of IDH wildtype glioblastoma patients. Acta Neuropathologica Communications 7:89 Online: View Source org/10.1186/s40478-019-0745-z

On December 13, 2021 Poseida Therapeutics, Inc. (Nasdaq: PSTX), a clinical-stage biopharmaceutical company utilizing proprietary genetic engineering platform technologies to create cell and gene therapeutics with the capacity to cure, reported interim results from its Phase 1/2 PRIME clinical trial of P-BCMA-101 for the treatment of relapsed/refractory multiple myeloma (R/R MM) at the 2021 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, Poseida Therapeutics, DEC 13, 2021, View Source [SID1234596958]).

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The results show that P-BCMA-101, a non-viral transposon-based autologous CAR-T, was well tolerated and demonstrated strong anti-tumor activity in advanced, late line R/R MM patients. The learnings from P-BCMA-101 informed the development of the Company’s first allogeneic program, P-BCMA-ALLO1 which is also being evaluated in R/R MM patients. The Company previously announced that it is winding down the P-BCMA-101 autologous program in favor of the allogeneic program, P-BCMA-ALLO1.

"We are encouraged by the outcomes seen from our clinical trial of P-BCMA-101, results that continue to validate our approach and that have informed P-BCMA-ALLO1, our first fully allogeneic CAR-T program for patients with multiple myeloma, as well as our other programs. Our focus is on creating differentiated product candidates with a high percentage of T stem cell memory (Tscm) cells," said Eric Ostertag, M.D., Ph.D., chief executive officer of Poseida Therapeutics. "Looking ahead, we continue to advance P-BCMA-ALLO1 and P-MUC1C-ALLO1 and look forward to presenting data in 2022 for both of these allogeneic programs."

The PRIME trial is a Phase 1/2, open label 3+3 single dose escalation of P-BCMA-101 CAR-T cells. The primary objective of the study is to determine the safety and maximum tolerated dose of P-BCMA-101 based on dose limiting toxicities (DLT), and the key secondary objective is to assess the anti-myeloma effect of the product. The median patient age was 62, with a median time since diagnosis of approximately 5.8 years. Patients were heavily pre-treated, with a median of 7 prior lines of therapy (2-18). As of the data cut-off date of October 15, 2021, a total of 98 patients have been dosed with P-BCMA-101.

The best observed treatment regimen was a combination with rituximab (n=14), with an overall response rate (ORR) of 78%, a VGPR/sCR rate of 43% and 100% overall survival at the time of the data cutoff. Progression free survival was also improved with rituximab, with median overall survival rates not yet reached in several cohorts including the rituximab combination cohorts. Response rates for other cohorts are consistent with results previously reported.

Across the study, no dose-limiting toxicities were observed. 28% of patients developed cytokine release syndrome (CRS) and 7% of patients developed neurotoxicity. None of the patients developed Grade 3 or higher CRS, and 2% of patients developed Grade 3 neurotoxicity. There were no treatment-related deaths among the patient population and no patients needed ICU admission as a result of CAR-T related toxicities. 28 patients were treated on a fully outpatient basis.

"P-BCMA-101 demonstrated strong anti-tumor activity in advanced multiple myeloma patients, and cohorts to date have shown minimal CRS and neurotoxicity, which allows for safe administration in an outpatient environment and combinations with other therapies," said Caitlin Costello, M.D., Associate Clinical Professor of Medicine and member of the Division of Blood and Marrow Transplantation at the University of California, San Diego. "These data indicate that the piggyBac transposon-based platform is an attractive option for allogeneic CAR-T cells, which has led to a first-in-human Phase 1 study."

The Company’s first fully allogeneic CAR-T cell product, P-BCMA-ALLO1 utilizes Poseida’s proprietary piggyBac DNA delivery system and Cas-CLOVER site-specific gene editing system to create an allogeneic product that prevents both graft-vs-host and host-vs-graft diseases and also incorporates a next-generation BCMA binder. P-BCMA-ALLO1 manufacturing involves a proprietary "booster" molecule that allows for numerous doses to be produced from a single manufacturing run, while maintaining desirable Tscm cells, which can reach percentages in the 60-80% range.

The Investigational New Drug (IND) application for P-BCMA-ALLO1 was given a safe to proceed designation by the FDA in August 2021. The Phase 1 study is an open label, dose escalation study following a 3+3 design of dose escalation in subjects with R/R MM. The study will assess the safety and maximum tolerated dose of P-BCMA-ALLO1 based on dose limiting toxicities. Key secondary objectives of the study include the anti-myeloma effect and safety of P-BCMA-ALLO1.

On December 13, 2021 Viracta Therapeutics, Inc. (Nasdaq: VIRX), a precision oncology company targeting virus-associated malignancies, reported the presentation of new preclinical data on vecabrutinib, a reversible inhibitor of Bruton’s tyrosine kinase (BTK) and interleukin-2-inducible kinase (ITK), in oral and poster presentations at the 2021 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, Viracta Therapeutics, DEC 13, 2021, View Source [SID1234596984]).

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The oral presentation featured preclinical data indicating that vecabrutinib may enhance the efficacy and safety of CD19-targeted chimeric antigen receptor T (CART19) cell therapy. Though CART19 cell therapy has been shown to effectively treat certain hematological malignancies, rates of long-term durable response after therapy are low and the majority of patients develop resistance. Additionally, CAR T-cell therapies are associated with significant safety concerns such as cytokine release syndrome and neurotoxicity.

Key findings from the oral presentation include:

Vecabrutinib increased the cytotoxic activity of CART19 cells and maintained their proliferation capacity
Vecabrutinib enhanced CART19 cell anti-tumor activity in a murine mantle cell lymphoma model
Vecabrutinib reduced the level of pro-inflammatory cytokines known to cause toxicities associated with CAR T-cell therapy; these observations were consistent with data from a prior Phase 1 clinical trial evaluating vecabrutinib as a treatment for patients with B-cell malignancies
In a direct comparison with ibrutinib, only vecabrutinib continued to induce CAR-T cell proliferation at high doses
"These compelling preclinical findings demonstrate the potential of vecabrutinib to improve the efficacy of CAR T-cells while ameliorating many of the concerns that currently prevent their use outside of inpatient settings," said Ayman Elguindy, Ph.D., Chief Scientific Officer of Viracta. "If translated to the clinic, the positive effects of vecabrutinib could potentially expand the use and tolerability of CAR T-cell therapies and improve the outlook for patients with a variety of cancers."

In addition to the oral presentation, a poster presentation detailed preclinical findings of vecabrutinib in a murine model of sclerodermatous cGVHD, a complication occurring in patients following allogeneic stem cell transplantation. Data showed that vecabrutinib significantly reduced cGVHD symptoms including skin irritation, redness, alopecia, and diarrhea via modulation of pathogenetic B- and T-cell subsets.

Ivor Royston, M.D., President and Chief Executive Officer of Viracta, commented, "We believe vecabrutinib’s differentiated reversible kinase inhibitory profile and ability to modulate immune-related signaling pathways give it the potential to overcome the shortcomings of ibrutinib when combined with CAR T-cell therapy. Looking ahead, we are strategically evaluating clinical development options to assess the combination of vecabrutinib and CART19 cell therapy."

A copy of the ASH (Free ASH Whitepaper) presentations will be available by visiting the Events and Webcasts page of the Viracta website following the conference’s conclusion.

About Vecabrutinib

Vecabrutinib is a well-tolerated, selective, reversible, non-covalent inhibitor of Bruton’s tyrosine kinase (BTK) and interleukin-2-inducible kinase (ITK). Vecabrutinib is being studied as a potential enhancer of efficacy and safety of CAR T-cell therapy.