On April 22, 2021 NRG Oncology reported that The first National Institutes of Health (NIH) National Cancer Institute (NCI)-funded clinical study examining stereotactic body radiotherapy (SBRT) in the treatment of oligometastatic breast, prostate, and non-small cell lung (NSCLC) cancers displayed evidence that SBRT can be safely used to treat patients who have multiple metastases (Press release, NRG Oncology, APR 22, 2021, View Source [SID1234578397]). These results were recently published in JAMA Oncology.

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The results of the Phase I NRG-BR001 trial, conducted by the NCI National Clinical Trials Network group NRG Oncology, indicate that SBRT treatment in standard doses was safe for 35 evaluable patients with a median of 3 metastases. There were no dose-limiting toxicities and over 50% of trial participants were alive at 2 years following treatment.

"Prior to this trial, little to no evidence was available to support that SBRT is a safe and tolerable treatment option for patients who have multiple metastases. Researchers have hypothesized that SBRT could improve survival outcomes for this patient population; however, it was imperative we determine the safety of this procedure, appropriate dose and scheduling, and how to coordinate across multiple centers the quality assurance of the procedures prior to testing its efficacy," stated Steven J. Chmura, MD, PhD, of the Department of Radiation and Cellular Oncology at the University of Chicago Comprehensive Cancer Center and the lead author of the NRG-BR001 manuscript. "To ensure safety, this trial used an extensive radiation QA process to test the accuracy of treating moving tumors and was the first NRG trial to require the use of 3D image guidance during treatment for soft tissue tumors."

NRG-BR001 enrolled up to 6 evaluable patients for each of the following 7 selected anatomic locations: bone/osseous (BO), spinal/paraspinal (SP), peripheral lung (PL), central lung (CL), abdominal/pelvic (AP), mediastinal/cervical lymph node (MC), and liver (L).As a single patient could contribute to more than one location, the safety question was able to be answered with 35 evaluable patients from the 42 enrolled trial participants. Patients were required to have 3-4 metastases or 2 metastases in close proximity to each other. SBRT starting dose was 50 GY over 5 fractions for the CL and MC groups, 45 GY over 3 fractions for the PL, AP, and L groups and 30 Gy over 3 fractions for the BO and SP group. Additional patients would be accrued as needed at defined de-escalated doses if any of the starting doses were not deemed to be safe.

The 35 evaluable patients had breast (n=12), NSCLC (n=10), and prostate (n=13) cancers. No dose de-escalations were needed. There were 8 instances of grade 3 adverse events. There were no treatment-related deaths.

SBRT for multiple metastases is now utilized in multiple ongoing Phase II and III NCI-sponsored trials. Follow-up research should be done in long surviving oligometastatic patients.

"These are important data from the multicenter study, confirming that complicated stereotactic body radiotherapy to multiple sites is safe and feasible. We eagerly await the results of ongoing, larger randomized trials to demonstrate how effective this is when compared to drug therapy alone for metastatic cancer," stated Mitchell Machtay, MD, the Associate Dean for Clinical Cancer Research at the Penn State College of Medicine and the interim Group Chair for NRG Oncology.

NRG Oncology BR001 was supported by grants UG1CA189867 (NRG Oncology NCORP), U10CA180868 (NRG Oncology Operations), U10CA180822 (NRG Oncology SDMC), U24CA180803 (IROC) from the National Cancer Institute (NCI).

Citation
Chmura S, Winter KA, Robinson C, Pisansky TM, Borges V, Al-Hallaq H, Matuszak M, Park SS, Yi S, Hasan Y, Bazan J, Wong P, Yoon HA, Horton J, Gan G, Milano M, Sigurdson ER, Moughan J, Salama JK, White J. The Safety of Stereotactic Body Radiotherapy (SBRT) for the Treatment of Multiple Metastases: Findings from the NRG Oncology NRG-BR001. JAMA Oncol. doi:10.1001/jamaoncol.2021.0687. [Epub ahead of print].

On April 22, 2021 Insmed Incorporated (Nasdaq:INSM), a global biopharmaceutical company on a mission to transform the lives of patients with serious and rare diseases, reported that it will release its first quarter 2021 financial results on Thursday, May 6, 2021 (Press release, Insmed, APR 22, 2021, View Source [SID1234578386]).

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Insmed management will host a conference call for investors beginning at 8:30 a.m. ET on Thursday, May 6, 2021 to discuss the financial results and provide a business update.

Shareholders and other interested parties may participate in the conference call by dialing (833) 340-0284 (domestic) or (236) 712-2425 (international) and referencing conference ID number 2257423. The call will also be webcast live on the company’s website at www.insmed.com.

A replay of the conference call will be accessible approximately two hours after its completion through June 5, 2021 by dialing (800) 585-8367 (domestic) or (416) 621-4642 (international) and referencing conference ID number 2257423. A webcast of the call will also be archived for 90 days under the Investor Relations section of the company’s website at www.insmed.com.

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.