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Nordic Nanovector Announces Initial Results from LYMRIT 37-05 Phase 1 Trial of Betalutin® in Relapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL)

On June 22, 2021 Nordic Nanovector ASA (OSE: NANOV) reported that encouraging initial results from the LYMRIT 37-05 Phase 1 trial investigating Betalutin (177Lu lilotomab satetraxetan) in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) not eligible for stem cell transplantation (Press release, Nordic Nanovector, JUN 22, 2021, View Source [SID1234584254]).

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The initial results from the completed Phase I study (n=16 treated with Betalutin) show that Betalutin was well tolerated, with a good safety profile consistent with all previous studies with Betalutin. As reported previously, a single, reversible dose-limiting toxicity (DLT) was seen in the last cohort investigating the highest dosing regimen (20 MBq/kg Betalutin and 100 mg/m2 lilotomab), which on review by the Independent Review Committee (IRC) resulted in three additional patients being enrolled. No further DLTs were seen. Clinical activity of Betalutin was seen in 6 evaluable patients receiving the highest dosing regimen including one complete response and one partial response.The IRC commented that the safety and anti-tumour activity of the highest dosing regimen could be considered for investigation in combination with other therapies used in R/R DLBCL which the Company is now evaluating, with an emphasis on combination partners that would not compromise the current safety profile of Betalutin.

Peter Braun, Nordic Nanovector CEO, commented: "We continue to be very encouraged by the overall safety profile that Betalutin exhibits in even the most fragile and highly pre-treated NHL patients. We have also seen clinical activity in DLBCL patients from a single administration of Betalutin and we will now consider the next steps for its development in this large patient population potentially in combination with other therapies, as part of our overall strategy to develop Betalutin for difficult to treat haematological tumours. Our near-term focus remains very much on completing PARADIGME in 3rd-line follicular lymphoma and delivering top line 3-month data by the end of 2021."

About LYMRIT 37-05

The LYMRIT 37-05 study is a Phase 1 open-label, single-arm, dose-escalation study designed to assess the safety and preliminary anti-tumour activity of a single administration of Betalutin. Patients were enrolled at clinical trial sites in the US and Europe. More information on this study can be found at www.clinicaltrials.gov (NCT02658968).

The starting doses of Betalutin and lilotomab were 10MBq/kg and 60mg (Cohort 1, n=3), respectively, and then Betalutin 10MBq/kg and lilotomab 100mg (Cohort 2, n=3 treated with Betalutin). Cohort 3 received 15MBq/kg and lilotomab 100mg (n=3) and Cohort 4 received 20MBq/kg and lilotomab 100mg (n=7 treated, 6 evaluable).

About DLBCL

DLBCL is an aggressive form of non-Hodgkin’s Lymphoma (NHL) that accounts for up to 43% of all NHL cases, making it the most common form of the disease. Approximately 40% of DLBCL patients relapse after first-line combination treatment with rituximab and chemotherapy and only 30-40% of relapsed patients respond with subsequent high-dose chemotherapy followed by Stem Cell Transplantation (ref. 1). There are currently very few therapeutic options for patients not eligible for SCT, which makes relapsed DLBCL a serious unmet medical need. The number of diagnosed incident cases of DLBCL in the 7 major markets (U.S., and key 5 European markets and Japan) was 64,172 in 2018 and is expected to be 74,927 in 2028 (ref. 2). The value of the 3L DLBCL market segment in the key 7 pharma markets is expected to increase from USD 0.6B in 2019 to USD 1.3B in 2028, the value of the 2L DLBCL market segment is expected to increase from USD 0.4B in 2019 to USD 2.0B in 2028. (ref. 2).

1. L.S. Raut and P. P. Chakrabarti: Management of relapsed-refractory diffuse large B cell lymphoma (2014) South Asian J. Cancer 3(1): 66–70

2. NHL and CLL Report, CRG, 2000, Disease Landscape and Forecast

Pionyr and Abcam extend partnership to evaluate TREM2-expressing cells in cancer patients

On June 22, 2021 Pionyr Immunotherapeutics, Inc., a company developing first-in-class antibody therapeutics that increase the body’s anti-tumor immunity and Abcam (AIM: ABC) (NASDAQ: ABCM), a global innovator in life science reagents and tools, reported the extension of their collaboration with a new commercial licensing agreement to support the progression of PY314, the first to the clinic of Pionyr’s compounds (Press release, Pionyr Immunotherapeutics, JUN 22, 2021, View Source [SID1234584252]).

Currently in Phase 1 clinical study[1], PY314 is an anti-TREM2 (Triggering Receptor Expressed on Myeloid cells 2) monoclonal antibody for the treatment of advanced solid tumors. PY314 is designed to tune the tumor microenvironment by selectively depleting immune suppressive TREM2-expressing tumor-associated macrophages to promote anti-tumor immunity.

Pionyr’s Phase 1 clinical study will recruit patients with predefined tumor types where macrophages expressing TREM2 in the tumor microenvironment are most likely implicated as a driver of resistant metastatic disease. Under the terms of the agreement, Pionyr will evaluate Abcam’s anti-TREM2 antibody to detect the presence of TREM2-expressing macrophages in tumor biopsy samples from patients enrolled in the first-in-human study. Pionyr will explore the potential for developing a companion diagnostic test leveraging Abcam’s high quality reagents and end-to end-expertise to facilitate and de-risk the diagnostics development journey.

Kevin Baker, SVP and Chief Development Officer at Pionyr, said: "We are excited to collaborate with Abcam to support the clinical development of our PY314 program for the treatment of solid tumors. Abcam’s in-depth knowledge and track record of successfully supporting diagnostic assay development is invaluable to anticipate late-stage development requirements, and to facilitate access to the right expertise at the right time."

John Baker, SVP Business Development at Abcam, said: "Pionyr’s Phase 1 PY314 is a promising therapy that has the potential to unlock durable benefits for cancer patients. Precise monitoring of the presence of TREM2 in tumor biopsy samples throughout the clinical development process, enabled by Pionyr’s use of Abcam’s EPR20243 clone, will provide vital support to the success of the trial. We are thrilled to be working with Pionyr and supporting their efforts to enhance the immune system’s anti-tumor response."

[1] Study of PY314 in Subjects With Advanced Solid Tumors – NCT04691375

Sintilimab in Combination with Chemotherapy Meets Overall Survival Primary Endpoint in the Global Phase 3 ORIENT-15 Study for the First-Line Treatment of Esophageal Squamous Cell Carcinoma

On June 22, 2021 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of oncology, metabolic, autoimmune and other major diseases, reported that the Phase 3 ORIENT-15 study met the predefined overall survival primary endpoint. ORIENT-15 is a global randomized, double-blind, multi-center clinical study evaluating sintilimab in combination with chemotherapy (cisplatin plus paclitaxel or cisplatin plus 5-fluorouracil [5-FU]) for the first-line treatment of patients with unresectable, locally advanced recurrent or metastatic esophageal squamous cell carcinoma (ESCC) (Press release, Innovent Biologics, JUN 22, 2021, View Source [SID1234584250]).

Based on an interim analysis conducted by the Independent Data Monitoring Committee (IDMC), sintilimab in combination with chemotherapy demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of overall survival (OS) compared to placebo in combination with chemotherapy regardless of PD-L1 expression status. The safety profile of sintilimab in this study was consistent with that observed in previously reported studies of sintilimab, and no additional safety signals were identified. These results will be presented at an upcoming medical meeting.

The principal investigator of the ORIENT-15 study, Prof. Shen Lin from Peking University Cancer Hospital and Institute stated, "More than half of new and fatal cases of esophageal cancer in the world occur in China every year. In China, esophageal cancer is the fifth most commonly diagnosed cancer and the fourth leading cause of death from cancer, and squamous cell carcinoma (ESCC) is the predominant histologic type. Treatment options for people with ESCC are limited. Chemotherapy is currently the main treatment for ESCC and, in recent years, immunotherapy has brought new hope in the treatment of this type of cancer, with some PD-1 inhibitors receiving approval as a second-line treatment for patients with ESCC in China. We are encouraged by these interim results of the ORIENT-15 study which demonstrated that sintilimab in combination with chemotherapy prolonged overall survival in the first-line treatment of patients with ESCC, regardless of PD-L1 status."

Dr. Zhou Hui, Senior Vice President of Clinical Development of Innovent, stated: "The treatment options for locally advanced or metastatic ESCC are limited and represent a significant unmet clinical need. ORIENT-15 is the largest clinical study of sintilimab conducted by Innovent to date. Despite the COVID-19 pandemic, the joint effort of the study’s investigators and broader team have enabled us to reach this milestone. We would like to express our sincere gratitude to all the patients who participated in the ORIENT-15 study. We hope these results can help to provide a new treatment option for patients with ESCC."

About the ORIENT-15 Study

ORIENT-15 is a global randomized, double-blind, multi-center Phase 3 clinical study evaluating sintilimab in combination with chemotherapy (cisplatin plus paclitaxel or cisplatin plus 5-fluorouracil [5-FU]), compared to placebo in combination with chemotherapy, for the first-line treatment of unresectable, locally advanced recurrent or metastatic esophageal squamous cell carcinoma (ClinicalTrials.gov, NCT03748134). At the time of interim analysis, a total of 659 eligible patients were enrolled and randomly assigned into the experimental group or control group in a 1:1 ratio. Patients were enrolled regardless of PD-L1 status. The primary endpoints included overall survival in all randomized patients and overall survival in PD-L1 positive (defined as CPS ≥10) patients.

About Esophageal Squamous Cell Carcinoma (ESCC)

Esophageal cancer is one of the most common malignant tumors worldwide that begins in the inner layer (mucosa) of the esophagus, which connects the throat to the stomach. Based on GLOBOCAN 2020 estimates, approximately 600,000 new cases of esophageal cancer are diagnosed and approximately 540,000 deaths result from the disease globally. Esophageal cancer is the seventh most commonly diagnosed cancer and the sixth leading cause of death from cancer worldwide. More than half of new and fatal cases of esophageal cancer in the world occur in China. In China, it is estimated there were approximately 320,000 new cases of esophageal cancer diagnosed and approximately 300,000 deaths resulting from the disease in 2020. Esophageal cancer is the fifth most commonly diagnosed cancer and the fourth leading cause of death from cancer in China, which has a five-year survival rate of only 30 percent.

The two main types of esophageal cancer are squamous cell carcinoma (SCC) and adenocarcinoma. In China, SCC is the predominant histologic type – accounting for more than 90 percent of all esophageal cancer. Currently, first-line standard systemic therapy in China is chemotherapy based on platinum drugs for unresectable, locally advanced recurrent or metastatic ESCC. There have been a few PD-1 inhibitors recently approved for the second-line treatment of patients with ESCC.

About Sintilimab

Sintilimab, marketed as TYVYT (sintilimab injection) in China, is an innovative PD-1 inhibitor with global quality standards jointly developed by Innovent and Eli Lilly and Company. Sintilimab is an immunoglobulin G4 monoclonal antibody, which binds to PD-1 molecules on the surface of T-cells, blocks the PD-1 / PD-Ligand 1 (PD-L1) pathway, and reactivates T-cells to kill cancer cells. Innovent is currently conducting more than 20 clinical studies of sintilimab to evaluate its safety and efficacy in a wide variety of cancer indications, including more than 10 registrational or pivotal clinical trials.

In China, sintilimab has been approved for three indications, including:

The treatment of relapsed or refractory classic Hodgkin’s lymphoma after two lines or later of systemic chemotherapy
In combination with pemetrexed and platinum chemotherapy, for the first-line treatment of nonsquamous non-small cell lung cancer
In combination with gemcitabine and platinum chemotherapy, for the first-line treatment of squamous non-small cell lung cancer
Additionally, Innovent currently has regulatory submissions under review in China for sintilimab:

In combination with BYVASDA (bevacizumab injection) for the first-line treatment of hepatocellular carcinoma
The second-line treatment of squamous non-small cell lung cancer
Innovent also has two clinical studies that have met primary endpoint for sintilimab:

in combination with cisplatin plus paclitaxel or cisplatin plus 5-fluorouracil for the first-line treatment of esophageal squamous cell carcinoma
The second-line treatment for esophageal squamous cell carcinoma
In May 2021, the U.S. FDA accepted for review the Biologics License Application (BLA) for sintilimab in combination with pemetrexed and platinum chemotherapy for the first-line treatment of nonsquamous non-small cell lung cancer.

Sintilimab was included in China’s National Reimbursement Drug List (NRDL) in 2019 as the first PD-1 inhibitor and the only PD-1 included in the list in that year.

TRexBio Closes the Final Tranche of $59 Million Series A Financing to Advance Innovation in Tissue Immunobiology for the treatment of Cancer and Inflammatory Diseases

On June 22, 2021 TRexBio, a discovery stage company decoding human tissue immune biology to create revolutionary therapeutics, reported the successful close of the final tranche of a $59 million Series A financing (Press release, TRexBio, JUN 22, 2021, View Source [SID1234584249]). Proceeds from the financing will be used to expand the company’s unique discovery platform that maps human tissue regulatory T cell (Treg) behavior to dysregulation in disease, and to advance its six preclinical therapeutic programs. Investors include Eli Lilly and Company (Lilly), SV Health, Johnson & Johnson Innovation, Pfizer Ventures, and Alexandria Venture Investments.

"The continued support from our investors further validates our approach to creating breakthrough therapeutics," said Carol Gallagher, Pharm.D., Executive Chair of TRexBio, and former President and CEO of Calistoga Pharmaceuticals. "We look forward to working with our investors and our academic and industry collaborators as we continue to create and advance a robust pipeline that addresses serious illnesses including cancer and auto-immune diseases."

TRexBio also announced the appointment of Johnston Erwin as Chief Executive Officer, and Ovid Trifan, M.D., Ph.D., as Chief Medical Officer, as part of the company’s plan to accelerate growth. Johnston, a seasoned industry veteran with experience in business development, venture investment, collaboration management, and clinical and regulatory development, joins TRexBio after a 36 year career with Lilly. He most recently served as VP of Corporate Business Development leading Lilly’s internal venture portfolio.

"TRex is at the forefront of one of the most exciting new areas in immunobiology and tissue homeostasis," said Johnston. "The company has a significant foundation in place, with a compelling vision, dedicated team and robust science. I am excited to lead the company into its next stage of development and ultimately transform the lives of patients by bringing a new generation of immune-based therapies to the world."

Dr. Trifan brings more than 20 years of medical research experience to TRexBio. Most recently he was the Chief Medical Officer and VP of Development at Apexigen, a clinical stage biotech company focused on immuno-oncology. Prior to Apexigen he held senior roles in clinical research at leading pharmaceutical companies including Bristol Myers Squibb and Johnson & Johnson, where he contributed to the development of multiple successful oncology drugs. Dr. Trifan will lead the advancement of TRexBio’s oncology programs into the clinic by the end of next year.

Mr. Erwin and Dr. Trifan are joined on the management team by Chief Scientific Officer Melanie Kleinschek, DVM, Ph.D., who has led the development of TRexBio’s unique ‘deep biology’ discovery platform. The platform uses high-resolution profiling of human tissue, modern computational biology tools, a proprietary system to generate tissue-like Tregs and disease-relevant phenotypic assays to generate novel insights into human tissue biology.

TRexBio’s accomplishments to date include:

Foundational collaborations with Lilly and the University of California San Francisco.
Advancement of six preclinical therapeutic programs across immuno-oncology and inflammation, two of which are on track to name development candidates in the next 12 months.
Identification of more than 20 novel tissue-focused targets from its proprietary ‘deep biology’ platform
The company works with an internationally recognized team of founding scientific advisors, including

Michael D. Rosenblum, M.D., Ph.D., Professor of Dermatology, Vice Chair of Research UCSF, and Co-Founder of Delinia Therapeutics;
Houman Ashrafian, BM Bch, DPhil, Managing Partner at SV Health Investors and former VP, Head of Clinical Science at UCB;
Adil Daud, M.D., Professor, Department of Medicine, Hematology/Oncology Director Melanoma Clinical Research, UCSF;
Diane Mathis, Ph.D., Professor in the Department of Immunology at Harvard Medical School, and holder of the Morton Grove-Rasmussen Chair in Immunohematology; and
Allison Simmons, M.D., Ph.D., Professor of Gastroenterology and Director of the MRC Human Immunology Unit at the University of Oxford.

Personalis Announces NeXT Level Biomarkers Symposium

On June 22, 2021 Personalis, Inc. (Nasdaq: PSNL), a leader in advanced genomics for cancer, reported its inaugural event, NeXT Level Biomarkers Symposium, which will showcase novel research into emerging biomarkers using the Personalis NeXT Platform (Press release, Personalis, JUN 22, 2021, View Source [SID1234584247]).

This event will detail the latest research from Personalis as well as a case study done in collaboration with the Parker Institute for Cancer Immunotherapy. Presentations from Personalis will focus on recently published research into HLA loss of heterozygosity, neoantigen prediction, as well as Personalis’ novel composite biomarker, the Neoantigen Presentation Score (NEOPS). In addition, Dr. Theresa LaVallee will be presenting findings from the PRINCE trial based on data developed and analyzed in collaboration with Personalis.

The agenda for NeXT Level Biomarkers Symposium will cover:

Biomarker Discovery with ImmunoID NeXT Platform
Exploring HLA LOH with the DASH (Deletion of Allele-Specific HLAs) Algorithm
Neoantigen Binding Prediction and Biomarker Discovery with SHERPA
Composite Biomarkers and our Neoantigen Presentation Score (NEOPS)
Parker Institute Case Study: The PRINCE Trial
NeXT Liquid Biopsy Overview and Review of AACR (Free AACR Whitepaper) Data
NeXT Dx and Companion Diagnostics (CDx) with Personalis
"We are excited to share our latest technology and product advances with our partners," said Richard Chen, MD, Personalis CSO. "Given the complex biology underlying cancer progression and response to treatment, our mission at Personalis is to provide broader, more comprehensive molecular profiling and testing for each patient’s cancer, thereby giving biopharma, physicians, and patients the information they need for precision oncology now and with an eye to the future. These new technologies help further that mission."