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!

On July 18, 2023 Telix Pharmaceuticals Limited (ASX: TLX, Telix, the Company) reported that the first patient has been dosed in a Phase I study of the Company’s investigational targeted radiation therapy, TLX250, in combination with a Merck KGaA, Darmstadt, Germany (Merck) DNA-dependent protein kinase (DNA-PK) inhibitor candidate, peposertib (M3814) (Press release, Telix Pharmaceuticals, JUL 18, 2023, View Source [SID1234633297]). The study is being conducted in patients with solid tumours expressing carbonic-anhydrase IX (CAIX), a potential pan-cancer target.

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STARSTRUCK (ClinicalTrials.gov Identifier: NCT05868174) is a Phase Ib, open label, single-arm, multicentre dose escalation and dose expansion study to evaluate the safety profile, dosing and activity of TLX250 (177Lu-DOTA-girentuximab) in combination with the DNA damage response inhibitor (DDRi) peposertib, which is an inhibitor of DNA-PK. The target population is patients with CAIX-expressing solid tumours that are relapsed or refractory to standard therapies. Up to 80 patients will be assessed in this study in Australian sites.

The clinical hypothesis is that the combination of TLX250 and a DNA-PK inhibitor provides an enhancement in potency through their synergistic action on cancer cells. Targeted radiation effectively induces DNA damage in targeted cancer cells and the DNA-PK inhibitor may act to prevent the cell from repairing this damage, resulting in higher potency at lower doses. This hypothesis was confirmed in preclinical studies, conducted under a strategic research collaboration between Merck and Telix announced in 2019,[1] and provided evidence that the combined effect of Merck’s investigational DNA-PK inhibitor peposertib with Telix’s targeted radiation candidate has potential to significantly improve efficacy and reduce the required radiation dose for tumour reduction and remission, compared to targeted radiation alone.

Principal Investigator for the STARSTRUCK study, Professor Nat Lenzo, GenesisCare Group Clinical Director Theranostics said, "The treatment of advanced cancer can be extremely challenging. We are pleased to support the commencement of this study with Telix to help determine if there is a potential future clinical benefit regarding the combination of molecular targeted radiation and DNA-PK inhibitors."

Telix Chief Medical Officer, Dr. Colin Hayward stated, "Preclinical data has shown excellent combination response, which has potential to translate to additional response or more tolerable treatment regimens in patients. We would like to thank Prof. Lenzo and his clinical team at GenesisCare Murdoch, as well as the patients who will contribute to this important study."

Merck and Telix are continuing the initial scientific collaboration to further explore and optimise the combination of TLX250 or other next-generation targeted radiation therapy candidates with Merck’s DDRi compounds in preclinical studies.

About TLX250

TLX250 (177Lu-DOTA-girentuximab) is an antibody-based therapeutic platform that targets CAIX, a cell surface protein that is highly expressed in several human cancers, and is currently the subject of the STARLITE-1 (ClinicalTrials.gov Identifier: NCT05663710) and STARLITE-2 (NCT05239533) studies in combination with immunotherapy.[2] High CAIX tumour expression is generally correlated with poor prognosis.

Telix’s companion investigational diagnostic imaging agent TLX250-CDx (89Zr-DFO-girentuximab) was the subject of a successful global Phase III trial (ZIRCON trial, NCT03849118), which completed enrolment and reported positive top-line data during 2022.[3] Analyses of primary endpoints and key secondary endpoints of the ZIRCON trial were presented to the medical community for the first time at ASCO (Free ASCO Whitepaper) GU on 18 February 2023.[4] TLX250-CDx is currently being investigated in the Phase II STARBURST study (ClinicalTrials.gov Identifier: NCT05563272) exploring CAIX expression in patients with a diverse range of solid tumours for potential diagnostic and therapeutic applications.

On July 18, 2023 Mabwell (688062.SH), an innovative biopharmaceutical company with entire industry chain, reported that its clinical trial application of 9MW2921 for advanced solid tumor was approved by the National Medical Products Administration (NMPA) (Press release, Mabwell Biotech, JUL 18, 2023, View Source [SID1234633296]). 9MW2921 is developed by Mabwell’s novel antibody-drug conjugate plateform IDDC.

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9MW2921 is a next generation antibody-drug conjugate (ADC) developed by Mabwell based on IDDC (Interchain-Disulfide Drug Conjugate) plateform for the treatment of solid tumors. It is an innovative antibody molecule linked to a novel payload (TOP1i) by a novel linker with fully autonomous intellectual property right. When 9MW2921 enters the body, it can specifically bind to antigens on the cell membrane surface, be internalized and transferred to the lysosome, release cytotoxic drug, and induce the apoptosis of tumor cells.

9MW2921 is pharmaceutical characterized as stable structure, homogeneous composition, high purity, and it is suitable for industrial scale-up. Compared with ADCs of the same class under development at home and abroad, 9MW2921 is significantly improved and optimized in endocytic activity, plasma stability, drug release characteristics, bystander killing effect, etc. In vivo pharmacodynamic studies demonstrated that 9MW2921 had a better tumor killing activity. In animal safety evaluation models including cynomolgus monkeys and rats, the on-target and off-target toxicities of 9MW2921 were effectively controlled, indicating that 9MW2921 has good safety profile and pharmacokinetic properties.

Belonging to the TACSTD family, Trop-2 is a cell surface glycoprotein encoded by the TACSTD gene. It is expressed in normal tissues at low levels, while overexpressed in multiple malignant tumors. Trop-2 expression correlates with tumor aggressiveness. Trop-2 overexpression promotes the growth, proliferation, and metastasis of tumor cells.

Next generation antibody-drug conjugate plateform IDDC

Mabwell has developed multiple ADC technology plateforms, and its anti-Nectin-4 ADC (R&D code: 9MW2821) is currently in the phase II clinical study.

IDDC is a next generation ADC site-specific conjugate technology plateform independently developed by Mabwell. It is composed of multiple systematized core patent technologies including site-specific conjugate process DARfinity, special designed linker IDconnect, novel payload Mtoxin, and conditional release structure LysOnly.

The next generation ADCs developed based on the above systematic patent technologies will carry better structural homogeneity, quality stability, pharmacodynamics and tolerability. Currently, the IDDC plateform has been validated in several products under development. It is expected multiple ADC products will enter clinical development in 2023 and 2024.

On July 18, 2023 Rakuten Medical, Inc. (Rakuten Medical), a global biotechnology company developing and commercializing precision, cell-targeting photoimmunotherapy-based on its proprietary Alluminox platform, reported that it will host a virtual R&D Day on the preliminary safety and efficacy findings from its open-label Phase 1b/2 study of Alluminox treatment using ASP-1929 in combination with anti-PD-1 therapy in recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) (Press release, Rakuten Medical, JUL 18, 2023, View Source [SID1234633295]). The webinar will take place on Thursday, August 10, 2023 at 8:30 AM PT / 11:30 AM ET.

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The event will feature Ann M. Gillenwater, Professor, Department of Head and Neck Surgery, Division of Surgery, The University of Texas MD Anderson Cancer Center who will discuss the promising results of the novel combination and the potential implications for the current treatment landscape. Rakuten Medical’s management team will provide other business updates including, but not limited to, a Japan commercial update and the Global Phase 3 Trial of ASP-1929 in India.

Rakuten Medical’s technology consists of drug and device components and which Rakuten Medical hopes will become a potential 5th pillar of cancer treatment. The Alluminox platform has been shown in pre-clinical trials to target specific tumors as well as immunosuppressive cells for destruction with minimal effects on surrounding normal tissue.

ASP-1929 targeting EGFR is approved in Japan and has been marketed as Akalux since January 2021 for unresectable locally advanced or recurrent head and neck cancer. ASP-1929 received Fast Track designation from the U.S. FDA in January 2018, and is currently under investigation in a global Phase 3 clinical trial for recurrent head and neck cancer but outside of Japan, ASP-1929 has not yet been approved by any regulatory authority.

A live question and answer session will follow the formal presentation. Parties interested in participating in this event should click here to register and access the live webcast. Please note that practicing healthcare professionals and patients are not permitted to attend.

On July 18, 2023 Verismo Therapeutics, a clinical-stage CAR T company, Penn spinout, and pioneer of the novel KIR-CAR platform technology, reported that it has raised $17M in a second pre-Series A financing round (Press release, Verismo Therapeutics, JUL 18, 2023, View Source [SID1234633294]). The financing will support continued advancement of the clinical trial for SynKIR-110, a first-in-class KIR-CAR T cell immunotherapy candidate for solid tumors, and pre-clinical development of SynKIR-310, a KIR-CAR T cell immunotherapy therapeutic for blood cancers.

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The funding round was co-led by DongKoo Bio, HLB Innovation and HLB. The funding will be used to advance multiple programs targeting solid and liquid tumors. With this $17M investment Verismo will have secured a total of $50M in financing since launching in 2020.

About the KIR-CAR Platform
The KIR-CAR platform is a dual-chain CAR T cell therapy and has been shown in preclinical animal models to be capable of maintaining antitumor T cell activity even in challenging solid tumor environments. DAP12 acting as a novel costimulatory molecule for T cells, aids additional T cell stimulating pathways, further sustaining chimeric receptor expression and improving KIR-CAR T cell persistence. This continued T cell function and persistence can lead to ongoing regression of solid tumors in preclinical models, including those refractory to traditional CAR T cell therapies. Furthermore, the KIR-CAR platform can be combined with many additional emerging technologies, such as in vivo gene engineering, advanced cell manufacturing and reprogramming, combinational therapies, and even allogeneic cellular therapies to provide the next-generation multimodal targeted immunotherapy for patients in need.