On April 22, 2021 Avectas reported that it is leading a consortium which will invest €7.23 million, including €4.4 million awarded under the Irish Government’s Disruptive Technology Innovation Fund (DTIF), to develop a high-throughput scale of its proprietary cell engineering platform Solupore (Press release, Avectas, APR 22, 2021, View Source [SID1234578385]). With consortium partners Bluebridge Technologies and NIBRT, the project expands Avectas’ development towards commercialising an advanced large-scale, digitalised cell engineering platform optimised to manufacture ‘off-the-shelf’ cell-based therapies for cancer treatment.

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The Disruptive Technologies Innovation Fund (DTIF) is a €500 million fund established under Project Ireland 2040 and run by the Department of Enterprise Trade and Employment with support from Enterprise Ireland.

Headquartered in Ireland, with locations in Toronto, Canada and Cambridge, USA, Avectas collaborates with leading cell therapy businesses and research institutes to address their cell engineering challenges using its patented Solupore technology. Cell therapy is a rapidly evolving therapeutic approach for cancer. Immune cells are taken from donors, engineered to make them more effective and then administered to patients. This award will allow Avectas to expand its Solupore platform to manufacture next-generation allogeneic products that can be produced at scale for large numbers of patients.

Bluebridge Technologies will develop a digitalisation dimension for the platform through the project. They will design, build and test software components to underpin the manufacturing technology, highlighting the convergence of cell therapy manufacturing and digitalisation. NIBRT will test and validate the platform in the context of an end-to-end manufacturing process and will facilitate technology adoption by situating the Solupore platform at their world-class facilities. All parties will work synergistically to disrupt the manufacture and delivery of cell-based therapeutics to patients.

Avectas has previously won significant award support from the European Union (under the Horizon 2020 programme). The company is engaged in work programmes with several therapeutic companies and leading academic laboratories, including The Simon Laboratory at UC Davis, California, the Centre for Commercialization of Regenerative Medicine (CCRM) in Toronto and the new NK Cell Centre of Excellence at Karolinska Institute, Sweden.

Speaking today, Dr. Michael Maguire, CEO of Avectas, remarked, "cell-based therapies offer the extraordinary potential for the treatment of cancers, and we believe that our Solupore Platform will disrupt the current cell therapy manufacturing process and help make Ireland a world centre for this developing area". Prof. Niall Barron commented, ‘NIBRT is delighted to be involved in this exciting DTIF-funded project which will accelerate the development of transformative technology for manufacturing revolutionary new therapies which go beyond being just treatments and in many cases actually cure patients. This project is a perfect example of the innovation and ambition that exists in Ireland to be at the forefront of this exciting new field".

Garret Coady, CEO of Bluebridge Technologies, added, "BlueBridge Technologies is delighted to be part of this project, which will showcase the power and promise of digital technologies that have the potential, not only to enable the delivery of novel therapies but to do so viably, at scale."

Dr. Maguire thanked the Department of Enterprise, Trade and Employment for their support: "This is expensive but hugely valuable work which could not exist without the support of the Department and the DTIF. We are grateful for that support."

On April 22, 2021 The Leukemia & Lymphoma Society Therapy Acceleration Program (LLS TAP) reported five new investments aimed at speeding the development of new and improved immunotherapies for the treatment of blood cancers (Press release, The Leukemia & Lymphoma Society, APR 22, 2021, View Source;lymphoma-society-therapy-acceleration-program-lls-tap-announces-five-new-investments-supporting-next-generation-cell-therapies-and-a-novel-immune-checkpoint-inhibitor-301274791.html [SID1234578384]. LLS has dedicated more than $100 million over the past several decades, through both grants and TAP investments, to advancing pioneering approaches that harness cellular immunotherapies to fight blood cancers .

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"We are very proud of our role in bringing groundbreaking immunotherapies to patients, including chimeric antigen receptor (CAR) T-cell therapy, which harnesses the power of T cells to kill tumor cells," said Louis DeGennaro, Ph.D., LLS President and Chief Executive Officer. "Our TAP venture philanthropy initiative is investing in the next generation of immunotherapies to find cancer treatments that are even more effective, safer, longer-lasting, easier to use, and active against more types of cancer."

LLS TAP is a strategic venture philanthropy funding initiative to accelerate high-risk, innovative blood cancer therapeutics and change the standard of care in leukemia, lymphoma, and multiple myeloma. LLS TAP makes individual investments of up to approximately $10 million and offers insights to funded companies from its extensive knowledge of blood cancer indications, the treatment landscape, and the expertise of LLS staff. LLS TAP due diligence and investment credibility can help companies raise needed funds to drive clinical-focused research forward. Today’s investments include three companies that have novel immunotherapies in early human clinical trials and two companies with promising programs in preclinical development for blood cancers:

Caribou Biosciences, Inc, co-founded by CRISPR pioneer and Nobel Prize winner Jennifer Doudna, Ph.D., uses next-generation CRISPR genome editing technology, referred to as chRDNA, to develop "off-the-shelf" CAR T-cell therapies for hard-to-treat blood cancers. Off-the-shelf CAR T-cell therapies use healthy donor T cells instead of reengineering a patient’s own cells. This approach could make treatment less costly and immediately available to patients with rapidly progressing disease.

The company’s lead therapeutic candidate, CB-010, which targets the CD19 protein, is in a phase 1 clinical trial (ANTLER) for treatment of patients with relapsed or refractory non-Hodgkin lymphoma. The company is working on additional off-the-shelf CAR T-cell therapies targeting BCMA and CD371 proteins, which play key roles in multiple myeloma and acute myeloid leukemia, respectively. Caribou is also working on adding a CAR to induced pluripotent stem cells to differentiate them into "natural killer" or NK cells to create a new type of immune cell therapy called CAR-NK, which holds promise for the treatment of solid tumors and metastases in addition to blood cancers.

NexImmune, a company that benefitted from an initial TAP investment nearly four years ago and now received a second investment as part of the company’s initial public offering, is taking a different approach. The company’s Artificial Immune Modulation, or AIM platform, does not rely on genetic manipulation of T cells. Instead, it uses nanoparticles—specific tiny molecules—to directly activate the body’s T cells to fight specific types of cancer. The company has two novel products in phase 1 clinical trials; NEXI-001 to treat advanced acute myeloid leukemia or myelodysplastic syndrome, and NEXI-002 for the treatment of advanced multiple myeloma.

Immune-Onc Therapeutics is developing a novel type of myeloid immune checkpoint inhibitor. Their lead candidate, called IO-202, a first-in-class antibody targeting the immune inhibitory receptor Leukocyte Immunoglobulin-Like Receptor subfamily B (LILRB) member 4 (LILRB4, also knowns ILT3), has entered a phase 1 clinical trial for the treatment of advanced acute myeloid leukemia and chronic myelomonocytic leukemia. The company also plans to evaluate this compound in solid tumors soon. The company’s work builds on early research by Chengcheng (Alec) Zhang, Ph.D. at The University of Texas Southwestern Medical Center that was also funded by LLS grants. Checkpoint inhibitors work by ‘releasing the brake’ from the body’s own immune cells so that they can effectively attack cancer cells. In addition to their lead drug candidate, Immune-Onc has active preclinical programs targeting other members of the LILRB family including IO-108, a novel antagonist antibody targeting LILRB2 (also known as ILT4) which is currently in the IND-enabling stage, IO-106, a first-in-class anti-LAIR1 antibody, and other undisclosed programs for solid tumors and blood cancers.

CARISMA Therapeutics is a spin out company from the University of Pennsylvania (Penn), founded by Saar Gill, M.D., Ph.D. and Michael Klichinsky, PharmD, Ph.D., SVP of Research. Early work at Penn was supported in part by LLS grants. CARISMA is developing CAR-engineered macrophages, white blood cells that exert broad effects on the immune system, to infiltrate solid tumors, eat away at cancer and activate the adaptive immune system. Based on preclinical studies, the company’s highly differentiated CAR-macrophage (CAR-M) platform may have the potential to overcome challenges encountered by other cell therapies such as trafficking limitations to the tumor site, immunosuppressive tumor microenvironments and the heterogeneous expression of tumor-associated antigens. CARISMA is actively enrolling patients for its phase 1 clinical trial for CT-0508, a HER2-targeted CAR-M. CARISMA is also working closely with LLS TAP to develop one or more CAR-M therapies for blood cancers.

Abintus Bio is developing cutting-edge in vivo CAR therapies that allow for powerful CAR T cells to be generated directly in a patient’s body, eliminating the need for time-consuming and costly collection, engineering and re-infusion of patient T cells. The innovative Abintus approach aims to reprogram T cells inside the body to attack and eliminate tumors. This technology is currently in preclinical testing and could, if successful, improve patient access with an off-the-shelf profile while advancing patient outcomes.
"Funding from leaders like LLS TAP helps fuel the progress of our clinical development program, bringing next-generation treatments that much closer to patients," said Rachel Haurwitz, Ph.D., President and Chief Executive Officer of Caribou Biosciences. "We’re particularly excited to be working with LLS TAP because it gives us access to their deep knowledge of blood cancer and their network of patients and drug development experts."

"The LLS track record in accelerating lifesaving blood cancer treatments is unparalleled," said Lee Greenberger, Ph.D., LLS Chief Scientific Officer. "The continuity of our funding from preclinical through clinical research demonstrates our commitment to supporting innovative therapies as they move from the laboratory into practice."

"Since 2017, three TAP-supported therapies have been approved in the U.S.," added Lore Gruenbaum, Ph.D., VP of TAP. "TAP partnership provides companies with deep blood cancer expertise and increases their credibility with the investment community. We look forward to our ongoing partnerships with these five companies as we work together to provide new hope for patients."

On April 22, 2021 Shanghai Henlius Biotech, Inc. (2696.HK) reported that the New Drug Application (NDA) of serplulimab injection (HLX10), a novel anti-PD-1 monoclonal antibody (mAb), for the treatment of unresectable or metastatic microsatellite instability-high (MSI-H) solid tumors that fail to respond to the standard therapy, has been accepted by the National Medical Products Administration (NMPA) and proposed to be granted priority review (Press release, Shanghai Henlius Biotech, APR 22, 2021, View Source [SID1234578383]). Serplulimab is potentially to be the first anti-PD-1 mAb in MSI-H solid tumors in China. For this indication, patients are screened for specific MSI-H tumor markers, rather than classifying the tumor types, covering a wide range of cancer types. Henlius adopts the "Combo+Global" development strategy for serplulimab, focusing on indication differentiation and combination therapy, with a total of 10 clinical trials conducted worldwide.

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The co-leading principal investigator of serplulimab Phase 2 clinical trial in unresectable or metastatic microsatellite instability-high or mismatch repair-deficient (MSI-H/dMMR) solid tumors, Professor Shukui Qin of Cancer Center of Nanjing Jinling Hospital, said, "Serplulimab showed excellent anti-tumor activity in preclinical and early-stage clinical studies, and the results of the Phase 2 clinical study in MSI-H solid tumors also states the favorable safety and efficacy. We hope that this China-developed novel PD-1 inhibitor will be launched as soon as possible, so that more patients with solid tumors could be accessible to high quality immunotherapy new options."

Executive Director, Chief Executive Officer and President of Henlius, Mr. Wenjie Zhang, said, "Serplulimab is the core innovative mAb of Henlius. Focusing on combination immunotherapy and international clinical trials, we have built up a differentiation development strategy for the product. Steady progress has been made in all clinical studies. We are very grateful to all the subjects, physicians and colleagues that have contributed to the NDA acceptance of serplulimab. We will push forward the clinical process in more indications as soon as possible and look forward to benefiting more patients around the world."

Several pivotal Phase 3 clinical trials covering comprehensive cancer types with high incidence

With the "Combo+Global" strategy, steady progress has been made in the clinical studies of 2 monotherapies and 8 combination therapies of serplulimab with chemotherapy, in-house VEGF and EGFR targets mAbs. Henlius actively carries out combination therapies that cover a wide range of tumor types with high incidence such as lung cancer, esophageal cancer, hepatocellular cancer, gastric cancer, head and neck cancer, and implements differentiation clinical development based on the Chinese cancer characteristics. Among them, while there are few explorations in the gastric cancer neoadjuvant/adjuvant area of PD-1 inhibitors, Henlius has conducted Phase 3 clinical studies in this field, leading the clinical trial progress around the globe, with the aim of enabling gastric cancer patients to benefit from the early line of immunotherapy. What’s more, the company has achieved all-around layout in the first-line of lung cancer, and has entered pivotal Phase 3 clinical trials in first-line squamous non-small cell lung cancer (sqNSCLC), first-line non-squamous non-small cell lung cancer (nsqNSCLC) and first-line small cell lung cancer (SCLC). The NDA filing of HLX10 in combination with chemotherapy for the first-line treatment of sqNSCLC in China will also be expected in the second half of 2021.

The all-around international layout to benefit emerging markets

The manufacturing and development of serplulimab is strictly in accordance with international standards and its manufacturing facility based in Shanghai has passed the European Union (EU) and China GMP certification. Henlius developed the international layout for serplulimab, which has been approved for clinical trials in China, the United States, the EU and other countries and regions. About 2000 patients have been enrolled in China, Turkey, Poland, Ukraine, Russia, etc., which shows confidence and recognition on the quality of the product in the international market. Apart from conducting international trials of HLX10, Henlius also actively seeks for international cooperation opportunities with the aim of benefiting more patients in the world, especially patients in emerging markets. Henlius has reached a collaboration agreement with PT Kalbe Genexine Biologics (KG Bio), upon which KG Bio is granted exclusive rights to develop and commercialize serplulimab in relation to its first monotherapy and two combination therapies in 10 Southeast Asian countries.

With the continuous development of the "Combo+Global" strategy, Henlius continues to build a diversified pipeline of innovative drug candidates with serplulimab as the lead, actively accelerating innovation and improving innovation efficiency, and committing to bringing affordable and high-quality innovative biologics to patients around the world.

About MSI-H solid tumors

The defect of mismatch repair (MMR) that can lead to base mismatch or insert in microsatellites during DNA replication, and the accumulation of incorrect bases usually causes microsatellite instability (MSI)[1]. MSI-H often occurs in several cancer types, such as endometrial cancer, colorectal cancer, gastric cancer, renal cell carcinoma, ovarian cancer, etc[2]. Studies have revealed that the prevalence of MSI-H across all tumor types is 14%[3]. Patients who suffer from this disease usually have higher response rates for immune checkpoint inhibitors[4-5]. Thus, MSI-H is becoming a more and more important biomarker for the immunotherapy predictions of patients with solid tumors. If the patient is MSI-H positive and meets the treatment criteria, the corresponding immunotherapy can be carried out without screening tumor sites and pathological classification, which aligns with the advanced concept of precision medicine and is applicable to a wide range of cancer types. Currently, the U.S. Food and Drug Administration (US FDA) has approved PD-1 target mAb for the treatment of second-line MSI-H/dMMR advanced solid tumors and first/second-line MSI-H/dMMR colorectal cancers. While there are still no anti-PD-1 mAb approved for MSI-H/dMMR advanced solid tumors in China, the treatment needs are far from being met.

On April 22, 2021 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) (the "Company" or "Jazz") reported the pricing of the previously announced offering (the "Offering") of $1.5 billion in an aggregate principal amount of 4.375% senior secured notes due 2029 (the "Notes") by Jazz Securities Designated Activity Company, a direct wholly owned subsidiary of the Company (the "Issuer") (Press release, Jazz Pharmaceuticals, APR 22, 2021, View Source [SID1234578382]). The Notes will mature on January 15, 2029 and will bear an interest rate of 4.375%. The Notes will be guaranteed by the Company and certain of its subsidiaries. The Offering is expected to close on April 29, 2021 subject to customary closing conditions.

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The aggregate principal amount of the Notes to be issued in the Offering decreased to $1.5 billion from the anticipated $2.7 billion announced on April 20, 2021, a decrease of $1.2 billion. This reduction corresponds to the equivalent anticipated increase in term loan borrowings under our new senior secured credit facilities (the "New Senior Secured Credit Facilities") in connection with the previously announced proposed acquisition of GW Pharmaceuticals plc ("GW") (the "Acquisition") from $2.65 billion to approximately $3.85 billion.

The Company expects to use the net proceeds from the Notes and Acquisition date borrowings under the new senior secured credit facilities, together with cash on hand to fund the cash consideration payable in connection with the Acquisition of GW, the refinancing of certain of the Company’s indebtedness (including the Company’s existing senior secured credit facility) and fees and expenses in connection with the foregoing. The Offering is not conditioned on the closing of the Acquisition. If (1) the Acquisition is consummated without the Company entering into the New Senior Secured Credit Facilities, (2) the Acquisition has not been consummated on or before August 3, 2021 (or such later date to which such date may be extended pursuant to the terms of the Transaction Agreement, dated February 3, 2021, among the Company, GW and Jazz Pharmaceuticals UK Holdings Limited (the "Transaction Agreement") or (3) the Transaction Agreement is terminated in accordance with its terms, the Issuer will be required to redeem all of the Notes at a redemption price equal to 100% of their principal amount plus accrued and unpaid interest to, but excluding, the redemption date.

The Notes will be offered and sold only to persons reasonably believed to be qualified institutional buyers pursuant to Rule 144A under the U.S. Securities Act of 1933, as amended (the "Securities Act") that are located in the United States, Canada, France, Ireland, Luxembourg, the United Kingdom, and Bermuda and to certain non-U.S. persons outside the United States pursuant to Regulation S under the Securities Act that are located in Canada, France, Ireland, Luxembourg, the United Kingdom, and Bermuda. The Notes have not been registered under the Securities Act or any state securities law and may not be offered or sold in the United States absent registration or an applicable exemption from the registration requirements of the Securities Act and applicable state laws.

This press release does not constitute an offer to sell or a solicitation of an offer to purchase the Notes or any other securities and does not constitute an offer, solicitation or sale in any state or jurisdiction in which such an offer, solicitation or sale would be unlawful.

On April 22, 2021 DermTech, Inc. (NASDAQ: DMTK) ("DermTech"), a leader in precision dermatology enabled by a non-invasive skin genomics platform, reported the launch of DermTech PLAplusTM, its next generation test for the enhanced early detection of melanoma (Press release, DermTech International, APR 22, 2021, View Source [SID1234578381]). PLAplus delivers objective and actionable information to guide clinical management decisions for skin lesions suspicious of melanoma.

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The new PLAplus test adds TERT (Telomerase Reverse Transcriptase) promoter DNA driver mutation analyses to the current RNA gene expression based Pigmented Lesion Assay (PLA), which includes LINC00518 and PRAME. TERT is individually associated with histopathologic features of aggressiveness and poor survival in melanoma. The combined tests (LINC00518 and PRAME, plus TERT) elevate the sensitivity from 91%1 to 97% and maintain a negative predictive value of >99%, resulting in a less than 1% probability of missing melanoma2,3. By combining RNA gene expression and DNA mutation analyses, PLAplus provides a highly accurate non-invasive genomic test for enhanced early melanoma detection.

"Identifying melanoma at its earliest stages provides patients with the highest cure rate, and TERT promoter mutations are independently associated with poor overall survival and more aggressive disease," said Laura Ferris, M.D., Ph.D., Associate Professor, Dermatology, University of Pittsburgh and senior author of Risk Stratification of Severely Dysplastic Nevi by Non-Invasively Obtained Gene Expression and Mutation Analyses.2 "Having additional genomic information to objectively assess disease risk beyond what can be ascertained visually can help physicians make an earlier, more accurate diagnosis."

"DermTech is thrilled about the addition of DNA TERT promoter mutation analyses to our test menu for the enhanced early detection of melanoma," said Claudia Ibarra, chief operating officer at DermTech. "As always, it is our commitment to deliver high quality testing and laboratory services to our patients and clinicians, and PLAplus is a prime example of this."

The National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology recognize the use of pre-diagnostic non‑invasive genomic patch testing for melanoma, like the DermTech PLATM, to help guide biopsy decisions for lesions suspicious of melanoma. There are over 21 peer reviewed publications summarizing its clinical validity and utility of the DermTech PLATM in studies of over 7,000 patients.

The lowest sensitivity of DermTech PLA demonstrated in our clinical studies to date
Jackson SR et al. J of SKIN. 2020; 4(2):124-129
Gerami P et al. J Am Acad Dermatol. 2017;76(1):114- 120.e2