On September 24, 2024 Shanghai Junshi Biosciences Co., Ltd (Junshi Biosciences, HKEX: 1877; SSE: 688180), a leading innovation-driven biopharmaceutical company dedicated to the discovery, development, and commercialization of novel therapies, and its wholly-owned subsidiary, TopAlliance Biosciences Inc. (TopAlliance Biosciences), reported that the European Commission (EC) has approved toripalimab (European trade name: LOQTORZI) for the treatment of two indications (Press release, Shanghai Junshi Bioscience, SEP 24, 2024, View Source [SID1234656134]):

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Toripalimab in combination with cisplatin and gemcitabine for the first-line treatment of adult patients with recurrent, not amenable to surgery or radiotherapy, or metastatic nasopharyngeal carcinoma (NPC);
Toripalimab in combination with cisplatin and paclitaxel for the first-line treatment of adult patients with unresectable advanced, recurrent, or metastatic oesophageal squamous cell carcinoma (ESCC).
In July, a positive opinion was issued by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) for the marketing authorization application (MAA) of these two indications. This approval applies to all 27 member states of the European Union, Iceland, Norway and Liechtenstein, making toripalimab the first and only drug in Europe for the treatment of NPC and the only first-line treatment for advanced or metastatic ESCC, regardless of PD-L1 status.

NPC is a malignant tumor that occurs in the nasopharyngeal mucosal epithelium and is one of the most common types of head and neck cancers globally. According to GLOBOCAN 2022 statistics, the number of newly diagnosed NPC cases in 2022 exceeded 120,000 worldwide. Due to the location of the primary tumor, surgery is rarely an option. The latest European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Guidelines recommend immunotherapy combined with chemotherapy as the first-line treatment for recurrent or metastatic NPC.

The approval of the NPC indication is primarily based on the results from the JUPITER-02 study (a randomized, double-blind, placebo-controlled, multinational multi-center Phase III clinical study, NCT03581786). The JUPITER-02 study is the first international multi-center, double-blind, randomized Phase III clinical study in the field of immunotherapy for NPC with the largest sample size, and the world’s first Phase III clinical study with preset statistical verification (Type I error control) for Overall Survival ("OS") for first-line immunotherapy combined with chemotherapy for NPC compared to chemotherapy alone and demonstrated a survival benefit. The study results were presented in an oral report during the Plenary Session of the 2021 annual meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) (#LBA2) and were subsequently featured on the cover of Nature Medicine. The results were also published in full in the Journal of the American Medical Association (JAMA). The results showed that, compared to chemotherapy alone, toripalimab in combination with chemotherapy reduced the risk of disease progression by 48% and the risk of death by 37%. The median progression-free survival ("PFS") in the toripalimab plus chemotherapy group was prolonged by 13.2 months compared to chemotherapy alone, from 8.2 months to 21.4 months. In addition, patients treated with this combined therapy achieved a higher objective response rate (ORR), longer duration of response (DoR), and higher disease control rate (DCR), and no new safety signal was identified. Long-term survival follow-up data, presented at ASCO (Free ASCO Whitepaper) 2024, reported a 5-year survival rate of 52.0%.

EC is one of the most common malignant tumors in the alimentary tract. According to GLOBOCAN 2022 statistics, esophageal cancer is the 11th most commonly diagnosed cancer and the seventh leading cause of cancer death worldwide, with over 511,000 new cases and over 445,000 deaths in 2022. ESCC and esophageal adenocarcinoma are the two main histological subtypes of esophageal cancer. The ESMO (Free ESMO Whitepaper) Guidelines recommend PD-1 blocking antibodies combined with chemotherapy for the treatment of patients with advanced or metastatic ESCC with PD-L1 positive status.

The approval of the ESCC indication is primarily based on the results from the JUPITER-06 study (a randomized, double-blind, placebo-controlled, multi-center Phase III clinical study, NCT03829969). The study aimed to evaluate the efficacy and safety of toripalimab in combination with paclitaxel/cisplatin (TP) for the first-line treatment of advanced ESCC compared with placebo in combination with chemotherapy. The results were first presented in an oral session during the ESMO (Free ESMO Whitepaper) Congress 2021 and later published in Cancer Cell and Journal of Clinical Oncology, two leading international oncology journals. The results of the study showed that toripalimab in combination with chemotherapy resulted in superior PFS and OS in patients with advanced or metastatic ESCC, the median OS was prolonged by 6 months to 17 months and the risk of disease progression or death in patients was significantly reduced by 42%. Futhermore, there was significant improvement in survival benefits regardless of PD-L1 status.

Professor Ruihua XU, Principal Investigator and President of Sun Yat-sen University Cancer Center, said, "Both NPC and EC are highly prevalent in Asia, while the development of innovative therapies for these cancer types has been slow in Europe and the Americas. The outstanding results from the JUPITER-02 and JUPITER-06 studies reflect the pioneering leadership of Chinese researchers in the diagnosis, treatment, and clinical research of NPC and EC. We hope that this ‘Chinese Solution’ will truly transform the outlook for patients around the world who have long lacked effective treatment options for these cancers, and bring them renewed hope for survival!"

Dr. Jianjun ZOU, General Manager and CEO of Junshi Biosciences, said, "‘In China, For Global’ has been a core strategic goal of Junshi Biosciences since its inception. The approval of toripalimab by the EC signifies that, following our success in China and the US, our global commercial strategy has officially expanded into Europe. It also reflects the international recognition of our research and production quality for innovative drugs. Moving forward, we will continue to collaborate with our partners on the commercialization of toripalimab in Europe, and provide high-quality, innovative therapies from China to more patients worldwide."

Dr. Patricia Keegan, Chief Medical Officer of TopAlliance Biosciences, said, "Junshi Biosciences and TopAlliance Biosciences are dedicated to producing innovative therapies that offer survival benefits to patients around the world while consistently addressing the clinical needs of local populations. This approval represents another significant milestone in our entry into the global market. In addition to toripalimab, we have several promising indications and drugs under development internationally. We believe that our commitment to providing patients with more effective treatment options will continually motivate us toward becoming a leading international innovative enterprise."

On September 24, 2024 Araris Biotech AG ("Araris"), a Swiss oncology biotech company developing next-generation antibody drug conjugates (ADCs), reported it has entered into an Agreement with Innate Pharma ("Innate") (Press release, Araris Biotech, SEP 24, 2024, View Source [SID1234651284]). Under the agreement, Innate will assign its portfolio of patents related to its ADC transglutaminase conjugation technology to Araris.

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"We are excited to acquire Innate’s portfolio of transglutaminase related patents, as this transaction further positions Araris as a leader in the development of ADCs using transglutaminase conjugation technology," said Dragan Grabulovski, Ph.D., CEO and co-founder of Araris. "We look forward to continuing to develop next-generation sitespecific ADCs and believe this acquisition not only expands our intellectual property portfolio, but also strengthens our competitive edge."

The newly acquired patents encompass a broad range of intellectual property that cover use of bacterial transglutaminase in conjugating various linker-payloads to antibodies.

On September 24, 2024 Generate:Biomedicines ("Generate") reported a multi-target collaboration with Novartis (NYSE: NVS) to discover and develop protein therapeutics across multiple disease areas (Press release, Generate Biomedicines, SEP 24, 2024, https://generatebiomedicines.com/media-center/generatebiomedicines-announces-multi-target-collaboration-with-novartis [SID1234650142]). The collaboration leverages Generate’s proprietary generative AI platform, ​"The Generate Platform," to create potentially first- and best-in-class molecules through AI-based optimization and de novo generation.

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The collaboration will combine The Generate Platform, which integrates machine learning with high-throughput experimental validation, with Novartis expertise and capabilities in target biology, biologics development, and clinical development to create novel therapeutics and to accelerate the pace of drug discovery and development.

"We are delighted to collaborate with Generate to explore the promise of generative AI in enhancing and accelerating the discovery of next-generation biologics," said Fiona Marshall, President of Biomedical Research at Novartis. ​"This collaboration offers an opportunity to leverage the unique strengths of our respective companies, from target biology and biologics discovery to machine learning/​AI and clinical development, in order to bring forward new medicines with transformative potential for patients."

"Partnering with a world-leading drug discovery and development organization like Novartis allows us to broaden the use of our cutting-edge generative biology platform to tackle even more areas of unmet medical need," said Mike Nally, Chief Executive Officer of Generate:Biomedicines. ​"We look forward to working closely with the team at Novartis to continue to demonstrate the transformative potential of programming biology to create better medicines for patients, faster."

Under the terms of the collaboration agreement, Generate will receive a total upfront payment of $65 million in cash from Novartis, which includes $15 million for the purchase of equity in Generate. Generate is also eligible to receive more than $1 billion in performance-based milestone payments, in addition to tiered royalties up to low double-digits. The number of targets and therapeutic areas are not being disclosed.

On September 24, 2024 Zetagen Therapeutics, a private, clinical-stage, biopharmaceutical company developing breakthrough therapies via local administration for metastatic and primary cancers to bone and other organs, reported publication of clinical data in the peer-reviewed Journal of the American Academy of Orthopaedic Surgeons (JAAOS) on ZetaFuse (Zeta-ZF-002)for the treatment of multi-level DDD in a Stage 4 lung cancer patient (Press release, Zetagen Therapeutics, SEP 24, 2024, View Source [SID1234647538]).

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"We are seeing promising consistency between our pre-clinical and clinical data with our ‘Zeta’ oncology platform," said Joe C. Loy, Chief Executive Officer of Zetagen. "This new data published in JAAOS further validates that our drugs in development with our proprietary formulations are producing the desired outcomes."

JAAOS Report Overview

The report, entitled Treating Multi-level Cervical Degenerative Disc Disease (DDD) in a Stage IV Lung Cancer Patient with Significant Comorbidities Using a Breakthrough Therapy focused on a 64-year-old, Stage 4, non-small cell lung cancer (NSCLC) patient with cervical DDD at three levels of the spine. The patient has several comorbidities which includes obesity and long-term smoking.

Due to a recent work-related accident which resulted in degenerative changes in the neck, the patient was referred for surgical consultation. Under an FDA Expanded Access protocol, (Compassionate Use) ZetaFuse (Zeta-ZF-002) was administered to promote bone formation in the patient’s three-level ACDF procedure. Despite the compromised health, ongoing chemotherapy treatments and poor bone physiology of the patient, case study results exceeded expectations, confirming radiographic fusion at all three cervical levels by eight months.

"Knowing the patient had been treated previously for his lung cancer with cytotoxic therapy and immunotherapy, which are known to negatively impact bone healing and, in spite of extensive exposure to these agents over the last three (3) years, our patient showed an excellent bone healing response to the novel, drug eluting biomaterial of the ZetaFuse," said Pedro Sanz-Altamira, MD, PhD, hematologist and oncology specialist at Dana Farber Cancer Institute who has been treating the case study patient for several years.

"Spine surgeons have no approved resources to treat cancer patients which have such orthopedic fusion needs, and we are pleased that this patient has seen outcomes which surpassed expectations in such a short period of time," said Nikhil Thakur, MD, Chief Medical Officer of Zetagen and Orthopaedic spine surgeon in Boston, MA.

View the JAAOS publication via open access here.

A New Approach to Treating Metastatic Cancer

Zetagen is dedicated to developing breakthrough therapies via local administration for metastatic and primary cancers to bone and other organs which may provide increased survival rates. The Company’s proprietary "Zeta" oncology platform is based on a novel, opioid growth factor receptor (OGFR) antagonist pathway which targets the management of the p21 transcript.

ZetaFuse (Zeta-ZF-002), the focus of the JAAOS publication, shares the same mechanism of action as Zetagen’s lead oncology drug candidate, ZetaMet (Zeta-BC-003), and were awarded separate Breakthrough Designations by the U.S. Food and Drug Administration (FDA) based upon their clinical indication. ZetaMet (Zeta-BC-003) is a synthetic, small-molecule, developed via a proprietary control release carrier developed to resolve metastatic breast cancer bone lesions, inhibiting pain while regenerating bone, with the potential to increase survival rates.

Peer-reviewed 2-year follow up data published in 2023 on ZetaMet (Zeta-BC-003) demonstrated resolution of lytic lesions, significant reduction in pain, prevention of vertebral fracture, and increased survival rate in a patient living with Stage 4 breast cancer.[i]

This patient had two groups of spinal lesions, a total of seven spinal lesions in all, one-group had two advanced lesions (T7 & L1) treated initially with fractionated radiation and when the cancer and pain returned, treated via an outpatient procedure with ZetaMet (Zeta-BC-003). Sixty (60) days later a second group of five new lesions appeared on the patient’s sacrum. She decided to forego fractionated radiation, the FDA approved a second procedure with ZetaMet (Zeta-BC-003), patient experienced significant reduction in pain (4x), and nine (9) months later independent radiologist reports showed no active tumor, no skeletal related events (SREs- fractures) in either lesion group, and the patient experienced complete resolution with the second lesion group with an increased survival rate of 36 months. View this publication via open access here.

"I am delighted to see these results being shared with our peers in scientific community," said Bryan Margulies, PhD, Chief Scientific Officer of Zetagen. "These observations build off of the extensive preclinical data we have generated over several years and we look forward to further advancing our ongoing human clinical trials as we continue to develop the ‘Zeta’ platform for patients living with metastatic and primary cancers."

[i] Pain Management. Volume 13, Issue 10, October 2023, Pages 569-577 View Source

On September 24, 2024 Silexion Therapeutics Corp. (NASDAQ: SLXN) ("Silexion" or the "Company"), a clinical-stage biotech developing RNA interference (RNAi) therapies for KRAS-driven cancers, reported significant new findings from its Phase 2 trial of LODER in patients with non-resectable locally advanced pancreatic cancer (LAPC) which bear the KRAS G12D or G12V mutation (approximately 70% of pancreatic cancer patients) (Press release, Silexion Therapeutics, SEP 24, 2024, View Source [SID1234646852]). Overall the updated analysis reveals a 56% objective response rate (ORR) in patients treated with LODER, with the ORR increasing to 67% in patients whose previously non-resectable tumors became resectable. This marks a significant step forward in potentially improving surgical outcomes for LAPC patients.

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Silexion had previously reported that patients treated with LODER in combination with standard-of-care (SoC) chemotherapy experienced a 9.3-month improvement in overall survival (OS) compared to chemotherapy alone. The new data now underscores LODERs additional potential to increase the resectability of tumors, opening up more surgical options for patients with otherwise inoperable pancreatic cancer.

Silexion is also progressing with the development of its next generation product, SIL-204, which builds upon the efficacy of the LODER. SIL-204 is designed to target a broader range of KRAS mutations, covering pan- G12x and G13D, as well as the previously reported findings of properties which should make it more effective clinically such as improved stability and enhanced ability to get to the site of action for silencing the KRAS oncogene. These improved properties demonstrated in preclinical models position SIL-204 as a promising option for the treatment of difficult-to-treat cancers such as locally advanced pancreatic cancer. Silexion continues to proceed with the development of this optimized candidate.

"We are very encouraged by these new findings, which demonstrate LODER’s ability to significantly improve tumor resectability in patients with non-resectable pancreatic cancer, and the improved profile of SIL-204" said Ilan Hadar, Chairman and CEO of Silexion. "As we advance our broader pipeline to address KRAS-driven cancers, this data further validates our oncogene silencing approach."

About the Phase 2 Trial of LODER

The open-label Phase 2 trial enrolled 48 patients in the mITT population with non-resectable locally advanced pancreatic cancer (LAPC) and borderline resectable pancreatic cancer (BRPC) across the U.S. and Israel. The trial was conducted in two parts:

Cohort 1 (n=29): Patients were randomized 1:1 to receive either LODER with SoC chemotherapy or SoC chemotherapy alone. The primary endpoint was overall survival (OS), with 16 patients confirmed to harbor the KRAS G12D/V mutation.
Cohort 2 (n=19): This cohort enrolled patients with non-resectable tumors, LAPC or BRPC, with the key endpoints focused on ORR and safety. Seven patients in this cohort were confirmed to have KRAS G12D/V mutations.
Objective Response Rate for 23 patients confirmed with KRAS G12D/V (Cohorts 1+2)