On October 31, 2024 Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. (the "Company") reported that the new drug application (NDA) (the "Application") based on the positive results from the pivotal phase III OptiTROP-Lung04 study of sacituzumab tirumotecan (sac-TMT, that it formerly SKB264/MK-2870) developed was accepted by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of China in adult patients with epidermal growth factor receptor (EGFR)-mutant locally advanced or metastatic non-small cell lung cancer (NSCLC) who progressed after treatment with EGFR-tyrosine kinase inhibitor (TKI) therapy (Press release, Kelun, OCT 31, 2024, View Source [SID1234647620]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

OptiTROP-Lung04 is a multi-center, randomized, registrational phase III clinical study that evaluates the efficacy and safety results of sac-TMT monotherapy versus pemetrexed plus platinum chemotherapy for the treatment of patients with EGFR-mutant locally advanced or metastatic NSCLC who progressed after treatment with EGFR- TKI therapy. At a pre-specified interim analysis, sac-TMT monotherapy demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of progression-free survival (PFS) as assessed by the blinded independent review committee (BIRC) compared with pemetrexed plus platinum chemotherapy. Sac-TMT also showed a manageable safety profile, with no unexpected safety signals identified.

The Application is the third NDA for sac-TMT that has been accepted by the NMPA. On October 25, 2024, it was announced on the official website of the CDE that the Application was planned to be included in the priority review and approval process of the CDE.

Previously, two NDAs for sac-TMT in patients with locally advanced or metastatic triple-negative breast cancer (TNBC) who have received at least two prior systemic therapies (at least one of them for advanced or metastatic setting) and for sac-TMT monotherapy in adult patients with locally advanced or metastatic EGFR-mutant NSCLC who experience progression following treatment with an EGFR-TKI and platinum-based chemotherapy, respectively, were accepted by the NMPA.

Sac-TMT, a core product of the Company, is a novel human trophoblast cell-surface antigen 2 (TROP2) antibody-drug conjugate (ADC) in which the Company has proprietary intellectual property rights, targeting advanced solid tumors such as NSCLC, breast cancer (BC), gastric cancer (GC), gynecological tumors, among others. Sac-TMT is developed with a novel linker to conjugate the payload, a belotecan-derivative topoisomerase I inhibitor with a drug-to-antibody-ratio (DAR) of 7.4. Sac-TMT specifically recognizes TROP2 on the surface of tumor cells by recombinant anti-TROP2 humanized monoclonal antibodies, which is then endocytosed by tumor cells and releases KL610023 intracellularly. KL610023, as a topoisomerase I inhibitor, induces DNA damage to tumor cells, which in turn leads to cell-cycle arrest and apoptosis. In addition, it also releases KL610023 in the tumor microenvironment. Given that KL610023 is membrane permeable, it can enable a bystander effect, or in other words kill adjacent tumor cells.

In May 2022, the Company licensed the exclusive rights to MSD (the tradename of Merck & Co., Inc., Rahway, NJ, USA) to develop, use, manufacture and commercialize sac-TMT in all territories outside of Greater China (includes Mainland China, Hong Kong, Macao, and Taiwan).

Dr. Micheal Ge, CEO of Kelun-Biotech, said, "sac-TMT (sacituzumab govitecan) has received its third NDA. In response to unmet clinical needs, the company has always adhered to the spirit of hard work inherent in Kelun, focusing on original innovation and doing practical work to develop new drugs with differentiated advantages and international potential. We believe that sac-TMT will shine in the field of oncology and contribute Chinese strength to the global health cause."

On October 31, 2024 CStone Pharmaceuticals (HKEX: 2616), an innovation-driven biopharmaceutical company focused on the research and development of anti-cancer therapies, reported that the UK Medicines and Healthcare products Regulatory Agency (MHRA) has approved sugemalimab in combination with platinum-based chemotherapy as a first-line treatment for adult patients with metastatic non-small cell lung cancer (NSCLC) without EGFR-sensitive mutations or ALK, ROS1, RET genomic alterations (Press release, CStone Pharmaceauticals, OCT 31, 2024, View Source [SID1234647619]). This marks the second overseas approval for sugemalimab following its recent authorization by the European Commission.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Dr. Jason Yang, CEO, President of R&D and Executive Director of the Board at CStone, said, "This approval is a significant milestone in our global expansion strategy. Sugemalimab is the first domestic anti-PD-L1 antibody to receive approval outside of China and has already entered the world’s second-largest pharmaceutical market, the EU. Now, with the UK approval, sugemalimab continued to expand its presence in the European market. The long-term survival data, recently presented at this year’s ESMO (Free ESMO Whitepaper) Congress, further confirmed sugemalimab’s value in the frontline treatment landscape for metastatic NSCLC."

Dr. Yang added, "We are actively pursuing additional partnerships across Western Europe, Latin America, the Middle East, Southeast Asia, and Canada, and expect to finalize some of these agreements shortly. Meanwhile, we are communicating with the European Medicines Agency (EMA) and other agencies for additional regulatory applications for other sugemalimab indications, including Stage III NSCLC, first-line gastric cancer, and first-line esophageal squamous cell carcinoma, aiming to bring innovative treatment options to more patients globally."

The MHRA’s approval is primarily based on the data from GEMSTONE-302, a multicenter, randomized, double-blind phase 3 trial. The study demonstrated that sugemalimab in combination with chemotherapy significantly prolonged progression-free survival (PFS) and overall survival (OS) compared to placebo combined with chemotherapy in treatment-naïve patients with metastatic NSCLC. Study results have been published in The Lancet Oncology and Nature Cancer, and have been presented at multiple international academic conferences in both oral and poster sessions.

On October 31, 2024 Kling Biotherapeutics ("Kling" or "the Company"), a biotech company developing antibody-based drugs for cancer and infectious diseases, reported that it will be presenting findings on its proprietary primary B-cell selection and evolution platform technologies, Kling-Select and Kling-Evolve at the Annual Protein & Antibody Engineering Summit (PEGS) Europe, held in Barcelona, Spain from 5-7 November 2024 (Press release, Kling Biotherapeutics, OCT 31, 2024, View Source [SID1234647618]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Poster one entitled ‘Highly efficient capture of circulating and tissue-infiltrating B cell repertoires from multiple species: Kling-Select,’ describes advances in Kling-Select, a proprietary B-cell immortalization platform developed to efficiently capture and screen B cells demonstrating its promise as an approach to the identification of both valuable new targets and therapeutic antibodies. Kling-Select is applied for the immortalization of B cells derived from human and animal sources such as camelid, rabbit, mouse, and non-human primates. The poster also highlights advances in the optimization of the fully integrated workflow allowing the discovery of functional monoclonal antibodies from primary B cells in as little as three weeks.

Poster two entitled ‘Kling-Evolve as a tool for rapid response to emerging variants and pandemic preparedness: directed evolution of variant-specific antibody from immortalized B cells,’ details the Kling-Evolve platform which enables the rapid ex vivo maturation of immortalized human B cells to identify neutralizing antibodies against escape variants. Kling-Evolve poses the potential for rapid development of countermeasures to combat and pre-emptively address evolving viruses amidst emerging pandemic threats.

Michael Koslowski, Chief Executive Officer at Kling Biotherapeutics, said: "Our technology is a powerful platform which is clinically validated, having been used to discover the fully human Respiratory Syncytial Virus (RSV) neutralizing antibody nirsevimab (Beyfortus – AstraZeneca / Sanofi). By using an ‘effective antibody first’ discovery approach, Kling’s platform technologies enable the discovery of relevant, completely novel antigen targets applicable to cancer as well as infectious diseases. Kling is well poised to develop next-generation antibody-based therapeutics to bring new, highly targeted treatments to cancer patients and address rising global concerns of the speed of response to emerging pandemic threats."

Details of the poster presentations are as follows:

Poster Title: Highly efficient capture of circulating and tissue-infiltrating B cell repertoires from multiple species: Kling-Select

Presenter: Casper Marsman, Senior Scientist – B Cell Platform Lead, Kling Biotherapeutics

Presentation Number: A073

Poster Title: Kling-Evolve as a tool for rapid response to emerging variants and pandemic preparedness: directed evolution of variant-specific antibody from immortalized B cells

Presenter: Alessandra Villa, Director of Discovery Platforms, Kling Biotherapeutics

Presentation Number: A074

Posters will be displayed in the Exhibit Hall at the following dates and times:

Tuesday, 5 November from 10:30 – 19:35 CET

Wednesday, 6 November from 10:30 -17:15 CET

Thursday, 7 November from 10:00 – 13:55 CET

On October 31, 2024 AbbVie (NYSE: ABBV) and EvolveImmune Therapeutics, an immuno-oncology company developing next-generation biotherapeutics to overcome the therapeutic challenges of cancer cell resistance to current immunotherapies, reported a collaboration and option-to-license agreement to develop multispecific biologics for multiple targets in oncology (Press release, AbbVie, OCT 31, 2024, View Source [SID1234647617]). The discovery partnership will leverage EvolveImmune’s T-cell engager platform to develop novel antibody-based therapies for solid and hematologic malignancies.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

EvolveImmune’s proprietary EVOLVE platform is designed to deliver potent, selective and integrated T-cell co-stimulation to amplify and sustain the tumor killing capacity of the T-cells. This approach aims to bypass low tumor immunogenicity, conditionally activate adaptive immunity and reduce T-cell dysfunction to overcome therapeutic challenges in solid and hematologic tumors.

"AbbVie is dedicated to advancing the understanding of devastating diseases like cancer and investing in groundbreaking technologies and therapeutic platforms, to deliver novel treatments for patients with high unmet needs," said Jonathon Sedgwick, Ph.D., senior vice president and global head of discovery research, AbbVie. "We are excited to collaborate with the talented team at EvolveImmune to further advance their novel T-cell engager platform technology."

"This collaboration with AbbVie, a global leader in oncology, offers tremendous validation of the EVOLVE platform and the dedicated and creative work of the EvolveImmune team," said Stephen Bloch, M.D., chief executive officer of EvolveImmune. "We believe that EVOLVE, with its differentiated CD2 co-stimulation strategy, represents a potential next-generation, best-in-class T-cell engager platform and that our technology may offer clinically meaningful benefits for patients."

Under terms of the agreement, EvolveImmune will receive $65 million in aggregate upfront fees and equity investment from AbbVie and is eligible for up to $1.4 billion in aggregate option fees and milestones, as well as tiered royalty payments on net sales.

On October 31, 2024 Intensity Therapeutics, Inc. ("Intensity" or "the Company") (Nasdaq: INTS), a late-stage clinical biotechnology company focused on the discovery and development of proprietary, novel immune-based intratumorally injected cancer therapies intended to kill tumors directly and increase immune system recognition of cancers, and The Swiss Group for Clinical Cancer Research SAKK ("SAKK"), a decentralized academic research institute that has been conducting clinical trials of cancer treatments in all major Swiss hospitals since 1965, reported they are collaborating in the INVINCIBLE-4 Study, a Phase 2 trial to treat patients with localized triple-negative breast cancer ("TNBC"), and announce that the first patient has been dosed in the study (Press release, Intensity Therapeutics, OCT 31, 2024, View Source;sakk-6622-302292937.html [SID1234647616]). The trial (NCT06358573) analyzes INT230-6 given before administration of the standard-of-care neoadjuvant immuno-chemotherapy ("SOC") and the SOC alone by using a 2-cohort design. The study evaluates the pathological complete response ("pCR") rates of the two cohorts relative to a null hypothesis, which is a pCR rate of ≤ 0.6. The success of each cohort in rejecting the null hypotheses will be evaluated.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The Phase 2 study is expected to enroll approximately 54 patients in Switzerland and France. The INVINCIBLE-4 Study is a randomized open-label, multicenter study to determine the clinical activity, safety, and tolerability of INT230-6 in patients with early-stage, operable TNBC who undergo SOC treatment and SOC alone. The primary endpoint is pCR in the primary tumor and affected lymph nodes. Patients will be randomized one to one to receive a regimen of either two doses of INT230-6 followed by SOC, which consists of pembrolizumab, anthracyclines, carboplatin, cyclophosphamide and paclitaxel, or to the SOC alone. The INVINCIBLE-4 Study initiation follows data reported from the Company’s INVINCIBLE-2 Study, where INT230-6 given alone showed tumor-killing properties at levels greater than 95% on a single intratumoral dose with systemic immune activation.

"Many TNBC patients undergoing SOC treatment alone fail to achieve a pathological complete response at the time of surgery, especially in larger tumor sizes. INT230-6 has the potential to fill this unmet need for aggressive subtypes, such as TNBC, through its anti-cancer mechanisms of action that cause tumor cell necrosis and ignite an anti-cancer immune-based response," said Andreas Mueller, M.D. Past-President of the Breast Cancer Group at the National Swiss Association for Clinical Cancer Research in Bern Switzerland and Head of Department of Medicine at the Kantonsspital in Winterthur and a supporting coordinating investigator for the study. "The ability for INT230-6 to induce necrosis and activate immune effects before a patient’s surgery without increases in toxicity would be a major advance for the treatment of breast cancer and potentially many other cancers."

"The majority of breast cancers are immune quiescent, resulting in minimal response to immunotherapies, and larger tumors are less responsive to therapy," said Ursina Zuerer-Haerdi, MD and Lead Physician for the Department of Medical Oncology and Hematology at the Cantonal Hospital in Winterthur, Switzerland and a supporting coordinating investigator on the study. "We have worked with Intensity to design a study for this novel intratumoral agent with the potential to increase the pathological complete response rates of the current best standard of care that would be clinically meaningful, and this trial is of high interest to SAKK’s physician network."

"INT230-6 is an innovative investigational product that combines cisplatin and vinblastine with a penetration enhancer molecule (SHAO)," said Markus Joerger, Prof. MD-PhD and Coordinating Investigator on the study and principal investigator for the Department of Medical Oncology and Hematology at the Cantonal Hospital St. Gallen. INT230-6 results in local immunogenic cell death when injected into the breast tumor, without systemic chemotoxicity but a high potency to induce systemic immunostimulatory effects. INT230-6 tackles the innate immune pathway that is not addressed by immune checkpoint inhibitors, and it is suggested to complement the systemic neoadjuvant backbone in study patients with early-stage TNBC which consists of chemotherapy and the checkpoint inhibitor pembrolizumab. We believe that the SAKK 66/22 study will provide crucial data to inform a large randomized clinical trial in patients with early-stage TNBC, a disease that is still burdened by substantial rates of fatal relapses following potentially curative treatment."

"We are excited to have initiated our Phase 2 study in presurgical triple-negative breast cancer. This study marks the first European patient treated with our drug – a new milestone. Triple-negative is a deadly and aggressive form of breast cancer, and patients having local disease currently undergo a harsh four to six-month regimen whereby a small percentage can die from the SOC before their surgery. Those patients who achieve a pCR have a lower risk of disease recurrence," said Intensity Therapeutics’ Founder, Chairman, and CEO, Lewis H. Bender. "We hope that by killing a substantial amount of the tumor upfront and increasing the immune response using INT230-6, we can increase the percentage of patients who achieve pCR and ultimately an improved event-free survival."

About INT230-6

INT230-6, Intensity’s lead proprietary investigational product candidate, is designed for direct intratumoral injection. INT230-6 was discovered using Intensity’s proprietary DfuseRx℠ technology platform. The drug comprises two proven, potent anti-cancer agents, cisplatin and vinblastine, and a penetration enhancer molecule (SHAO) that helps disperse potent cytotoxic drugs throughout tumors for diffusion into cancer cells. These agents remain in the tumor, resulting in a favorable safety profile. In addition to local disease control and direct tumor killing, INT230-6 has been shown to release a bolus of neoantigens specific to the malignancy, leading to immune system engagement and systemic anti-tumor effects. Importantly, these effects are mediated without immunosuppression, which often occurs with systemic chemotherapy.

About Triple Negative Breast Cancer in the Presurgical Setting

Approximately 11-17% of breast cancers test negative for estrogen receptors (ER), progesterone receptors (PR), and excess human epidermal growth factor receptor 2 (HER2) protein, qualifying them as triple negative. TNBC is considered to be more aggressive and has a poorer prognosis than other types of breast cancer, mainly because there are fewer available targeted medicines. Most patients with local TNBC typically receive immune/chemotherapy before surgery. Since the publication of Keynote-522, standard neoadjuvant treatment for TNBC includes systemic chemotherapy (anthracyclines, cyclophosphamide, paclitaxel, carboplatin) and the anti-PD-1 monoclonal antibody pembrolizumab. pCR rates are only 63%, with rates generally lower in the larger-sized T2 to T4 tumors. The toxicity of the Keynote-522 regimen is high, with 80% of patients experiencing grade 3 or higher treatment-related AEs, including treatment-related adverse events that lead to death in 0.5% of patients.