On July 18, 2023 ENB Therapeutics, Inc., a biotechnology company pioneering a new and differentiated class of therapeutics targeting the endothelin B receptor (ETBR) inhibitor, reported that the company has completed enrollment of its international Phase 1 ENBOLDEN-101 trial investigating the safety and efficacy of lead product ENB-003 in combination with KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy (Press release, ENB Therapeutics, JUL 18, 2023, View Source [SID1234633304]). The Phase ½a study is a multicenter, open-label study conducted in the US and Australia and is comprised of two parts. Part 1 recruited 46 patients and was a dose-escalation study to determine the recommended dose for the Part 2 expansion phase of the study. The results of this study will be presented by ENB Therapeutics in a poster titled, "ENB-003, an ETBR antagonist, in combination with pembrolizumab for refractory advanced solid tumors: Topline data from the ENBolden-101 Phase 1B study" at the Immuno-oncology Summit which is being held August 7-9, 2023 in Boston, Massachusetts.

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ENB-003 in combination with pembrolizumab was well tolerated in the dose escalation study and demonstrated no DLTs across the 6 dosing cohorts. The most common treatment emergent adverse events irrespective of grade or causality included fatigue (28.2%), constipation (26.1%), abdominal pain (26.1%), nausea (23.9%), anemia 17.4%, diarrhea (17.4%). Serious adverse events, grade 3 and above considered possibly related to study treatment included fatigue (n=4), diarrhea (n=3), dyspnea (n=3) constipation (n=2), rash (n=2). 15 patients with evaluable disease were enrolled in cohorts 1-5 (ENB-003 dose range 150ug-1000ug) and 15 patients with evaluable disease were enrolled in the 6th cohort (ENB-003 dose 2000ug). The dosing frequency for cohort 6 was doubled to 6 doses every 3 weeks from 6 doses every 6 weeks in cohort 1-5. The DCR across all cohorts irrespective of ETBR status was 33% (1 PR, 9 SD, 20 PD). The DCR in ETBR-Hi patients was 33% in cohorts 1-5 (4 SD, 1 PR, 10 PD) and 83% in cohort 6 (5 SD, 1 PD). The DCR for ETBR-Lo patients in cohort 6 was 0% (9 PD). ETBR-Lo patients were not enrolled in cohorts 1-5. For microsatellite stable (MSS) platinum refractory/ resistant ovarian cancer there was an 80% DCR across all cohorts (1 PR, 3 SD, 1 PD) with a trend for durable responses at higher doses of ENB-003. A platinum refractory MSS ovarian cancer patient experienced a 95% PR of 12-month duration. The sample size was not powered for statistical significance.

"The completion of enrollment of the Phase 1 ENBOLDEN-101 first-in-man study is a significant milestone for our Company. We are extremely encouraged by the results in heavily treated cancer patients refractory to standard of care treatment," stated Sumayah Jamal, MD-PhD, President, Chief Scientific Officer and Co-Founder of ENB Therapeutics. "Our data suggest potential efficacy in patients that do not historically respond to immunotherapy and support further clinical development. We are grateful to our patients and their families for their participation in our study. "

Part 2 is a dose expansion study at the recommended dose designed to evaluate the safety, tolerability and efficacy of ENB-003 in combination with pembrolizumab in cancers refractory to standard of care including MSS R/R ovarian cancer, MSS pancreatic cancer, anti-PD1 refractory HNSCC, anti-PD1 refractory melanoma and anti-PD1 refractory TNBC. For more information on this Phase 1/2a study, see NCT04205227.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

About ENB-003

ENB-003 is a selective endothelin B receptor (ETBR) inhibitor that, in preclinical studies, enhances efficacy of CAR-T and anti-PD-1 in solid tumors across multiple cancer types in preclinical studies. In an ongoing multi-center Phase 1/2 clinical trial, early efficacy signals suggest that ENB-003 overcomes resistance to the anti-PD-1 therapy KEYTRUDA (pembrolizumab) in heavily pre-treated drug resistant cancer patients. The Phase 2 portion of the ENB-003 + pembrolizumab combination study is expected to start in the first half of 2024. The trial will enroll microsatellite stable platinum refractory and primary platinum resistant ovarian cancer patients, as well as microsatellite stable pancreatic cancer patients that have failed standard of care.

On July 18, 2023 NorthStar Medical Radioisotopes, LLC, a global innovator in the development, production and commercialization of radiopharmaceuticals used for therapeutic applications and medical imaging, reported the signing of a supply agreement for the therapeutic medical radioisotope, actinium-225 (Ac-225) with Bayer (Press release, NorthStar Medical Radiostopes, JUL 18, 2023, View Source [SID1234633303]). Under the terms of the agreement, NorthStar will provide Bayer with its environmentally preferred, non-carrier added (n.c.a.) Ac-225. NorthStar’s Ac-225 will be used by Bayer for several of its radiopharmaceutical programs.

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Ac-225 is a high energy alpha-emitting radioisotope of increasing interest for clinical studies investigating the use of radiopharmaceutical therapy (RPT), which combines select molecules with therapeutic radioisotopes, such as Ac-225, to directly target and deliver therapeutic doses of radiation to destroy cancer cells in patients with serious disease. Ac-225 carries sufficient radiation to cause cell death in a localized area of targeted cells while limiting damage to nearby healthy tissue due to the short range of alpha radiation. NorthStar is positioned to be the first commercial-scale producer of n.c.a. Ac-225 for advancing clinical research and commercial radiopharmaceutical products. The Company will use its environmentally preferred electron accelerator technology to produce n.c.a. Ac-225 that is free of long-lived radioactive contaminants and byproducts associated with other production methods, which pose regulatory and waste management challenges for hospitals and health systems.

"We are very pleased to enter this Ac-225 supply agreement with Bayer, a global healthcare leader, and we look forward to working with them moving forward," said Frank Scholz, Ph.D., President and Chief Executive Officer, NorthStar Medical Radioisotopes. "Our companies share a vision of developing and delivering innovative technology and compounds to drive research and ensure clinical availability of targeted radiopharmaceutical therapies for patients with cancer and other serious diseases. As a company at the forefront of U.S. radioisotope production, we are applying our proven accelerator technology expertise with molybdenum-99 (Mo-99) and copper-67 (Cu-67) to rapidly advance large-scale production of n.c.a. Ac-225. The electron accelerator is installed and construction is progressing on schedule on our dedicated, state-of-the-art Actinium-225 Production facility, with initial production of radiochemical grade Ac-225 planned in 2024. NorthStar expects to submit a Drug Master File to the FDA as quickly as possible thereafter, which, upon acceptance by the FDA, will allow it to provide cGMP grade Ac-225."

On July 18, 2023 Therapeutic Solutions International, Inc. (TSOI), reported that its breast cancer focused immuno-oncology subsidiary, Res Nova Bio, Inc., has identified and filed a patent on a novel mechanism of action of its immunotherapy-enhancing product FloraStilbene (Press release, Therapeutics Solutions International, JUL 18, 2023, View Source [SID1234633302]).

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The Company has demonstrated that administration of FloraStilbene, which is a proprietary combination of pterostilbene and the active ingredient in the abortion pill, mifepristone, suppresses loss of T cell activity caused by growing breast cancer. In a series of experiments, it was demonstrated that FloraStilbene stopped degradation of a protein called "T cell receptor zeta chain" which has previously been shown to be inactivated by the enzyme caspase-31. Breast cancer patients with higher levels of T cell receptor zeta chain have been reported to possess superior survival as compared to patients with lower levels2.

"Breast cancer takes an incredible toll on patients, which I have witnessed firsthand," said Dr. James Veltmeyer, Chief Medical Officer of the Company, and co-inventor on the patent. "The data presented today, which is the basis for our proposed clinical trial, potentially will help to enhance efficacy of the brand-new type of medicine called ‘immunotherapy’ which to date has resulted in many cures of cancers which were previously considered incurable."

"Therapeutic Solutions International has a long history of advancing the field of cancer immunotherapy, dating back to 2015 when we filed our now issued patent # 9682047 entitled ‘Augmentation of oncology immunotherapies by pterostilbene containing compositions’ which covers the utilization of pterostilbene and various derivatives in increasing the therapeutic index of immunotherapy," said Timothy Dixon, President, and CEO of Therapeutic Solutions International and co-inventor. "I am honored to see the work led by Ms. Ramos which has advanced our science to the point where it is close to initiating clinical trials."

"Immunology has revolutionized cancer therapy. Now that the concept has been established that the immune system can be trained to kill cancer, it is time to optimize the existing medications whether they be proteins, cells, or oncolytic viruses," said Famela Ramos, President and CEO of Res Nova Bio and co-inventor. "Overcoming systemic immune defects induced by the cancer seems to us to be the first step in the optimization of immunotherapy. This is what we are aiming to accomplish in the clinical development of FloraStilbene.

On July 18, 2023 Hangzhou Qihan Biotech Co., Ltd. ("Qihan" or "Qihan Biotech" or "the Company"), an industry leader in applying multiplexable genome editing technology to cell therapies and organ transplantation, reported that the National Medical Products Administration (NMPA) approved its clinical trial application for the product QN-019a (Press release, Qihan Biotech, JUL 18, 2023, View Source [SID1234633301]). It is the first IND approved in China for a gene-edited iPSC-derived cell therapy product.

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Qihan Biotech utilizes multiplexable genome editing technology to modify human Induced Pluripotent Stem Cells (iPSCs) and differentiate them into natural killer (NK) cell therapy product QN-019a, targeting CD19-positive B-cell lymphoma. The clinical indication for QN-019a is CD19-positive relapsed/refractory aggressive B-cell non-Hodgkin lymphoma. According to the official website of the Center for Drug Evaluation, NMPA, the clinical trial application for QN-019a cell injection has received approval as of July 18, 2023.

"The approval of our application for the clinical trial is a result of our team’s collaborative efforts and also signifies Qihan entering a new phase in its evolution. The IND approval is the first step in a long drug development journey, and we will adhere to scientific rigor and fully use our genome editing technology and in-depth biological knowledge to continue our research," said Dr. Luhan Yang, the founder and CEO of Qihan Biotech. "We look forward to developing Off-the-Shelf cell therapy products with long-term efficacy for patients and realizing the vision of Qihan."

On July 18, 2023 Fosun Kite Biotechnology Co., Ltd., jointly established by Shanghai Fosun Pharmaceutical (Group) Co., Ltd. and Kite Pharma of the United States reported that Yikaida used for the treatment of adult large B-cell lymphoma (r/r LBCL) ("this new indication") who failed first-line immunochemotherapy or relapsed within 12 months conditionally approved by the State Drug Administration ("NMPA") (Press release, Fosun Kite Biotechnology, JUL 18, 2023, View Source [SID1234633299]). This also marks the official launch of Yikaida for second-line indication.

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Previously, there was no CAR-T cell therapy product in China for the treatment of adult large B-cell lymphoma who failed to respond to first-line immunochemotherapy or relapsed within 12 months after first-line immunochemotherapy. Fosun Kite’s Yikaida added a second-line indication. The approval for marketing of the drug has successfully promoted new progress in the treatment of adult large B-cell lymphoma, bringing hope to more patients who have failed or relapsed with first-line immunochemotherapy. At the same time, Yikaida is currently the first approved CAR-T cell therapy product in China for this new indication.

Professor Ma Jun from the Harbin Institute of Hematology and Oncology said, "The latest research shows that the incidence of lymphoma in China is increasing year by year. How to improve the prognosis of lymphoma treatment and improve the clinical cure rate has attracted the attention of the industry. If innovative therapy is limited to the later line, the curative effect will be discounted, and the patient’s benefit will be limited."

One of the shareholders of Fosun Kite, Kite, the global cell therapy leader, its ZUMA-7 study is the first head-to-head challenge salvage chemotherapy + autologous transplantation for LBCL patients with primary refractory or recurrence within 12 months after first-line treatment in the past 30 years, A large international multicenter RCT study. Based on Kite’s ZUMA-7 study, Axi-cel was approved by the FDA in April 2022 for the treatment of adults with LBCL who are refractory or have relapsed within 12 months of first-line treatment. The OS data of ZUMA-7 was announced at the American ASCO (Free ASCO Whitepaper) meeting in June this year. The median follow-up time was 47.2 months. The Axi-cel group did not reach the median OS, while the standard treatment (SOC) group was 31.1 months, and the HR value was 0.726, that is to say, the second-line use of Kite’s Axi-cel CART product reduced the risk of death by 27%.

"Lymphoma patients benefit from early use of CART therapy. All cancer drugs start from the end-line indications, and, after they are approved, continue to advance to the approval of second-line or first-line indications. It is because the treatment port can be brought forward. This is the law of new drug research and development." Professor Ma Jun said.

"China’s pharmaceutical industry is booming, and it is trying to innovate from multiple dimensions, from enterprises to supervision. The rapid approval of Yikaida as a second-line treatment for LBCL indications in China is a new milestone in the field of CAR-T cell therapy. The good news for lymphoma patients in China, and we look forward to bringing benefits to more patients." Professor Ma Jun said, "Axi-cel is the first choice for second-line treatment for patients with primary refractory or early relapsed LBCL, and it will greatly increase the cure rate. Significantly prolonging the Event-free survival (EFS) and OS of patients is a major therapeutic breakthrough in the field of lymphoma and will become the second-line standard treatment for applicable patients."

Yikaida has benefited more than 500 patients in the two years since its launch.

Adult large B-cell lymphoma (LBCL) is a common malignant lymphoma, accounting for about 30-40% of non-Hodgkin’s lymphoma. It has the characteristics of few treatment options, rapid disease progression, high mortality, and a short survival period. In recent years, the incidence rate in China has shown a rapid growth trend. In June 2021, Fosun Kite took the lead in launching the first domestic CAR-T cell therapy product——Yikaida (阿基仑塞Injection), from June 2021 to now, with personalized customization, one-time treatment, more than 500 patients with relapsed/refractory large B-cell lymphoma have brought revolutionary new breakthroughs in the field of cancer treatment in China.

On June 5, 2023, the ASCO (Free ASCO Whitepaper) annual meeting and the "New England Journal of Medicine" respectively introduced the main overall survival of the global multi-center phase III randomized controlled study ZUMA-7 (Kite’s MRCT study) in the form of oral reports and full-text releases. Period (OS) analysis results. When the median follow-up time was 47.2 months, compared with the second-line standard of care (SOC), 阿基仑塞 significantly improved the OS of patients, and the risk of death was reduced by 27.4%. It is worth mentioning that 57% of the patients in the SOC group received cell therapy in the third line or later. In this case, the median OS of the SOC group has been greatly improved, but the OS difference between the two is still statistically positive, which is very exciting.

"We are very happy to hear this good news, which indicates that Chinese patients can receive earlier treatment, which benefits patients and families," said Ms. Mei Jingping, Chairman of Fosun Kite.

Vice Chairman of Fosun Kite, Mr. Mert Aktar, commented, "This is a great milestone, and we believe it will benefit more Chinese patients, and bring hope to both patients and their families!"

Huang Hai, CEO of Fosun Kite, said: "Yikaida has treated more than 500 patients with relapsed/refractory large B-cell lymphoma since the second anniversary of its launch. With its excellent real-world curative effect, stable drug quality control, and continuous improvement. The availability of medicines has been highly recognized by the public. Here, we would like to express our gratitude and heartfelt thanks to the experts, scholars, and patient families and our Shareholders, Fosun Pharmaceutical (Group), and Kite Pharma, for their trust and support of Fosun Kate and Yikaida.

The approval of the new second-line indications of Yikaida is a key step taken by Fosun Kate and its shareholders to address China’s major unmet medical needs of lymphoma patients, and it is also a key step for China’s drug review and approval bureau. For the great efforts in the approval and supervision of innovative drugs, we would like to express our sincere gratitude to the government departments and regulatory agencies for their care and guidance at the glorious moment when new indications are approved!

To reach further & higher, we still need to make strides. Standing at the new starting point of the second anniversary of Yikaida’s commercialization, we look forward to Yikaida being able to cure more patients and improve their wonderful lives!