On September 23, 2024 Antengene Corporation Limited ("Antengene", SEHK: 6996.HK), a leading innovative, commercial-stage global biopharmaceutical company dedicated to discovering, developing and commercializing first-in-class and/or best-in-class medicines for cancer, reported that the Thailand Food and Drug Administration has approved a New Drug Application (NDA) for XPOVIO (selinexor) for two indications (Press release, Antengene, SEP 23, 2024, View Source [SID1234646829]): (1) In combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma(MM) who have received at least one prior therapy; and (2) in combination with dexamethasone for the treatment of adult patients with MM who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, two immunomodulatory agents and an anti-CD38 monoclonal antibody, and who have demonstrated disease progression on the last therapy.

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With a novel mechanism of action, XPOVIO is the world’s first approved orally-available, selective XPO1 inhibitor, which has already been approved in nine markets in APAC. This successful approval for XPOVIO in Thailand will introduce novel therapies to the clinical management of patients with MM in Thailand, benefiting many patients and their families in the country. To date, XPOVIO has also been included in national health insurance or reimbursement schemes in the mainland of China, Australia, Singapore and South Korea.

The ASEAN region, with its steady economic growth and a population exceeding 600 million, has become a significant potential market for global biomedical development. The accelerating aging population in ASEAN has increased the overall disease burden on patients and local communities, leading to a growing demand for novel therapeutics. Fulfilling its commitment to enhancing the health and well-being of the ASEAN population, Antengene has successfully obtained NDA approvals for XPOVIO in Malaysia in August and very recently in Thailand, and expects XPOVIO to be approved in Indonesia in the second half of 2024. Looking ahead, the company aims to introduce more innovative medicines to the ASEAN market, bringing improved healthcare to more patients in the region.

While bringing XPOVIO to more APAC markets, Antengene is also striving to expand the indications of XPOVIO. Leveraging the drug’s novel mechanism of action, Antengene is currently developing multiple combination regimens of XPOVIO for the treatment of various indications including myelofibrosis (MF), and endometrial cancer.

About XPOVIO (selinexor)

XPOVIO is the world’s first approved orally-available, selective inhibitor of the nuclear export protein XPO1. It offers a novel mechanism of action, synergistic effects in combination regimens, fast onset of action, and durable responses.

By blocking the nuclear export protein XPO1, XPOVIO can promote the intranuclear accumulation and activation of tumor suppressor proteins and growth regulating proteins, and down-regulate the levels of multiple oncogenic proteins. XPOVIO delivers its antitumor effects through three mechanistic pathways: 1) exerting antitumor effects by inducing the intranuclear accumulation of tumor suppressor proteins; 2) reducing the level of oncogenic proteins in the cytoplasm by inducing the intranuclear accumulation of oncogenic mRNAs; 3) restoring hormone sensitivity by activating the glucocorticoid receptors (GR) pathway. To utilize its unique mechanism of actions, XPOVIO is being evaluated for use in multiple combination regimens in a range of indications. At present, Antengene is conducting multiple clinical studies of XPOVIO in the mainland of China for the treatment of relapsed/refractory hematologic malignancies and solid tumors (3 of these studies are being jointly conducted by Antengene and Karyopharm Therapeutics Inc. [Nasdaq:KPTI]).

On September 23, 2024 Ryvu Therapeutics (WSE: RVU), a clinical-stage drug discovery and development company focusing on novel small molecule therapies that address emerging targets in oncology, reported that it will present its ONCO Prime drug discovery platform at the 6th Annual RAS-Targeted Drug Development Summit, a leading global end-to-end RAS therapies forum, which will take place on September 24-26 in Boston, MA (Press release, Ryvu Therapeutics, SEP 23, 2024, View Source [SID1234646827]).

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ONCO Prime is a cutting-edge drug discovery platform identifying novel synthetic lethal targets using patient-derived primary cell cultures. The platform comprises of new cancer models with the optimal ratio of translational potential and high-throughput feasibility. By using patient-derived cells, the ONCO Prime platform uses patients’ medical history combined with histopathological, genomic, and transcriptomic data to enable the correlation of clinical and molecular data. Initial platform screens have identified potentially novel drug targets in KRAS-mutant colorectal cancer (CRC). Additionally, the platform has broad applicability across multiple tumor types, and additional screens in other major tumor areas are ongoing.

Krzysztof Brzózka, Ph.D., Chief Scientific Officer and Executive Vice President of Ryvu Therapeutics, said:

– "We are proud that, within a short time since its development began in mid-2023, the ONCO Prime platform has already identified novel targets in KRAS-mutant cells – targets overlooked by conventional immortalized CRC cell lines. This achievement highlights the platform’s unique capability, and we’re excited to discuss its implications with the international RAS-focused community."

ONCO Prime is co-financed by the European Union under the Operational Programme European Funds for Modern Economy 2021-2027. Project title: "ONCO Prime: new possibilities for personalised anti-cancer therapy based on patient-derived primary cell cultures, omics characterisation, and functional assays". Grant Agreement no: FENG.01.01-IP.02-0095/23. This co-financing is being administered through the Polish Agency for Enterprise Development (PARP). Ryvu expects to receive PLN 26.3 million (approximately USD 6.6 million) in grant funding over five years to support ONCO Prime.
The 6th Annual RAS-Targeted Drug Development Summit is the central hub dedicated to every aspect of RAS discovery and development, from discovery and clinical development to commercialization. It equips 150+ global RAS leaders with the means to create effective RAS therapies for better patient outcomes.

On September 14, 2024 VerImmune Inc., ("VerImmune"), a venture-backed biotechnology company developing a groundbreaking Virus-inspired Particle (ViP) platform technology, reported the successful first closing of $4.5 million in its Pre-Series A financing round (Press release, VerImmune, SEP 23, 2024, View Source [SID1234646826]).

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The financing was led by Beiley Biofund, an early-stage venture capital firm focused on cutting-edge technologies that address high unmet medical needs. New investors, including Dr. John Ballantyne, PhD, co-founder and former CSO at Aldevron, participated in the round, alongside returning investors Proxima Ventures, Mana Ventures, Gaingels, and others.

"We are extremely pleased to have completed the first closing of our Pre-Series A round. This funding signals strong market recognition of the potential for novel modalities to address unmet medical needs," said Dr Joshua Wang, PhD, Founder and CEO of VerImmune Inc. "We intend to use this capital to advance our conviction that ViP-based therapeutics will open the door to an entirely new approach to immunotherapy and other therapeutic areas."

"We are very attracted by and delighted to invest in VerImmune’s Virus-inspired Particle (ViP), which is both non-viral and well differentiated. In many ways, it is technically superior to other virus-like particle modalities in addressing well recognized existing challenges. We are also impressed by the progress of the company and are confident in its future success," said Dr. Che Hsu, PhD, General Manager of Beiley Biofund.

"We are extremely pleased to continue our support for VerImmune. The company’s ViP technology offers a new class of ‘virally inspired’ proteins that can function as a non-viral delivery system. For the first time in drug discovery, there are now systematic and efficient ways to manipulate proteins and their geometry beyond the traditional rules in recent years," said Haolin Sung, MBA Partner at Proxima Ventures.

This closing also strengthens VerImmune’s Board of Directors with the addition of two seasoned executives with extensive experience in early-stage product development for novel modalities:

Dr. Che Hsu, PhD, General Manager of Beiley. Before joining Beiley, Dr. Hsu was a successful pharmaceutical life sciences executive with a strong track record of advancing programs from discovery through IND and beyond. He has held leadership roles at both early-stage startups and established companies such as Bristol Myers Squibb and Celgene, where he contributed to the development of innovative therapies. His experience spans both science and business, making him a valuable leader in the life sciences field. Dr. Hsu is also currently an MBA candidate in the Chicago Booth Executive MBA program at the University of Chicago.

Dr. Marta New, PhD, MBA, an experienced drug developer and former venture capitalist. Dr. New previously held leadership roles as a partner at Agent Capital, principal investor at Baxalta Ventures, and commercial lead at Baxter International’s Renal Franchise. She is currently the CEO of Radyus Research and will join VerImmune as an independent director.
"We are thrilled to welcome Dr. Hsu and Dr. New to our Board of Directors," said Dr Roger Pomerantz, MD, FACP, Chair of VerImmune’s Board. "Their expertise in novel modalities and deep industry knowledge will strengthen our strategic guidance and enhance our efforts toward clinical and commercial success."

VerImmune plans to utilize the funds to advance the development of its lead product candidate, VERI-101, towards clinical trials. VERI-101 is a First-in-class cancer immunotherapy that leverages the ViP to redirect pre-existing immune memory from cytomegalovirus (CMV) infection toward tumors for destruction. The company also aims to expand and accelerate strategic partnerships to unlock the potential of its ViP platform technology. One such collaboration is VerImmune’s ongoing research partnership with A*STAR’s Bioprocessing Technology Institute (BTI) in Singapore, which focuses on biomanufacturing process innovations.

On September 23, 2024 Astrazeneca reported high-level results from the TROPION-Breast01 Phase III trial of datopotamab deruxtecan (Dato-DXd) compared to investigator’s choice of chemotherapy, which previously met the dual primary endpoint of progression-free survival (PFS), did not achieve statistical significance in the final overall survival (OS) analysis in patients with inoperable or metastatic hormone receptor (HR)-positive, HER2-low or negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer previously treated with endocrine-based therapy and at least one systemic therapy (Press release, AstraZeneca, SEP 23, 2024, View Source [SID1234646825]).

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This analysis follows the positive PFS results presented at the 2023 European Society for Medical Oncology Congress which showed datopotamab deruxtecan demonstrated a statistically significant and clinically meaningful improvement in PFS. An improvement in patient-reported outcomes was also seen.1 The PFS data and additional results for key secondary endpoints were published this month in the Journal of Clinical Oncology.

The safety profile of datopotamab deruxtecan was consistent with that observed in the previous analysis including lower rates of Grade 3 or higher treatment-related adverse events compared to chemotherapy, and no new safety concerns identified. All grade interstitial lung disease (ILD) rates remained low with no new Grade 3 or higher ILD events observed.

With multiple antibody drug conjugates (ADCs) approved during the course of the trial, including Enhertu (trastuzumab deruxtecan), subsequent treatment following patients’ disease progression or treatment discontinuation is likely to have affected survival results.

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "The metastatic HR-positive breast cancer treatment landscape has advanced remarkably in the last several years to the benefit of patients. Based on the TROPION-Breast01 results, there is evidence of the clinical value of datopotamab deruxtecan in this setting. We will continue discussions with regulatory authorities and apply insights from these results to our clinical development programme for datopotamab deruxtecan in breast cancer."

Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo, said: "Datopotamab deruxtecan has previously shown a statistically significant progression-free survival benefit in TROPION-Breast01, a result supported by multiple meaningful secondary measures including patient-reported outcomes. We are proud to have brought forth a new standard of care for patients with metastatic breast cancer with Enhertu and we remain committed to making datopotamab deruxtecan another potential option for patients who can benefit."

Datopotamab deruxtecan is a specifically engineered TROP2-directed DXd ADC discovered by Daiichi Sankyo and being jointly developed by AstraZeneca and Daiichi Sankyo.

The data will be presented at a forthcoming medical meeting and shared with regulatory authorities currently reviewing applications for this indication.

In addition to TROPION-Breast01, AstraZeneca and Daiichi Sankyo are evaluating datopotamab deruxtecan alone and with immunotherapy as treatment for patients with triple-negative or HR-low, HER2-negative breast cancers in the TROPION-Breast02, TROPION-Breast03, TROPION-Breast04 and TROPION-Breast05 Phase III trials.

Notes

​HR-positive breast cancer
Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide.2 More than two million breast cancer cases were diagnosed in 2022 with more than 665,000 deaths globally.2 While survival rates are high for those diagnosed with early breast cancer, less than 35% of patients diagnosed with or who progress to metastatic disease are expected to live five years following diagnosis.3

Approximately 70% of diagnosed cases are considered what has been historically called HR-positive, HER2-negative breast cancer (measured as HER2 score of IHC 0, IHC 1+ or IHC 2+/ISH-).3 Endocrine therapies are widely given consecutively in the early lines of treatment for HR-positive metastatic breast cancer; however, after two lines of treatment, further efficacy from endocrine therapy is often limited.4 The current standard of care following endocrine therapy is chemotherapy, which is associated with poor response rates and outcomes.4-7

TROP2 is a protein broadly expressed in HR-positive, HER2-negative breast cancer and is associated with increased tumour progression and poor survival.8,9

TROPION-Breast01
​TROPION-Breast01 is a global, randomised, multicentre, open-label Phase III trial evaluating the efficacy and safety of datopotamab deruxtecan (6.0mg/kg) versus investigator’s choice of single-agent chemotherapy (eribulin, capecitabine, vinorelbine or gemcitabine) in adult patients with unresectable or metastatic HR-positive, HER2-low or negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have progressed on and are not suitable for endocrine therapy per investigator assessment and have received at least one additional systemic therapy for unresectable or metastatic disease.

Following disease progression or discontinuation of datopotamab deruxtecan or chemotherapy, patients had the option to receive subsequent treatment at the discretion of their physician. Crossover between trial arms was not permitted.

The dual primary endpoints of TROPION-Breast01 are PFS as assessed by blinded independent central review and OS. Key secondary endpoints include objective response rate, duration of response, investigator-assessed PFS, disease control rate, time to first subsequent therapy and safety.

TROPION-Breast01 enrolled more than 700 patients in Africa, Asia, Europe, North America and South America. For more information visit ClinicalTrials.gov.

​​Datopotamab deruxtecan (Dato-DXd)
​Datopotamab deruxtecan (Dato-DXd) is an investigational TROP2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, datopotamab deruxtecan is one of six DXd ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programmes in AstraZeneca’s ADC scientific platform. Datopotamab deruxtecan is comprised of a humanised anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

​​A comprehensive global clinical development programme is underway with more than 20 trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple cancers, including NSCLC, triple-negative breast cancer (TNBC) and HR-positive, HER2-negative breast cancer. The programme includes seven Phase III trials in lung cancer and five Phase III trials in breast cancer evaluating datopotamab deruxtecan as a monotherapy and in combination with other anticancer treatments in various settings.

On September 23, 2024 Lantern Pharma Inc. (NASDAQ: LTRN), an artificial intelligence ("AI") company developing targeted and transformative cancer therapies using its proprietary RADR AI and machine learning ("ML") platform with multiple clinical-stage drug programs, reported that the company has been granted three rare pediatric disease designations (RPDD) by the FDA (Press release, Lantern Pharma, SEP 23, 2024, View Source [SID1234646824]). Lantern was granted these rare pediatric disease designations in: malignant rhabdoid tumors (MRT), rhabdomyosarcoma (RMS), and hepatoblastoma.

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"At Lantern, we’re harnessing AI and data-driven approaches to revolutionize cancer drug development, aiming to dramatically reduce costs, accelerate timelines, and enhance precision in bringing new therapies to patients," stated Panna Sharma, CEO and President of Lantern Pharma. "Our recent breakthrough in identifying three additional, high-potential indications for LP-184 in pediatric cancers exemplifies this progress. We believe that ‘AI for good’ should address both blockbuster opportunities as well as rare, often overlooked pediatric cases. The FDA’s Rare Pediatric Disease designation for these three potential programs is a testament to this commitment. We’re acutely aware that patients and their families are relying on innovators like us to speed up therapy development. These designations mark a crucial step forward in advancing our expanding portfolio of pediatric programs targeting these devastating and rare cancers. It reinforces our dedication to transforming hope into tangible solutions for those who need them most."

Rare pediatric diseases are defined by the FDA as serious or life-threatening conditions primarily affecting children under 18, with fewer than 200,000 cases in the U.S. A key benefit of obtaining a RPDD is the potential to receive a priority review voucher following FDA approval of a product with RPDD if the marketing application submitted for the product satisfies certain conditions, including approval prior to September 30, 2026 unless changed by legislation. These vouchers, often called "golden tickets," can significantly expedite the review process for future NDAs or biologic license applications, reducing the standard review time from about ten months to six. Sponsors can either use these vouchers themselves or sell them to other companies. These vouchers, in the recent past, have commanded sales prices of approximately $100 million USD.

Lantern’s investigational drug candidate, LP-184, has shown preclinical activity in a wide range of solid tumors, garnering it multiple orphan and rare pediatric designations. LP-184 is currently in a multi-center Phase 1A clinical trial that is expected to enroll approximately 50 to 60 patients across a wide range of solid tumors. Based on the results and findings from this clinical trial and other collaborative studies, Lantern will plan and potentially develop future clinical trials for specific pediatric patients in ATRT, MRT, RMS and Hepatoblastoma.

About MRT – Malignant Rhabdoid Tumors

Malignant rhabdoid tumors are rare childhood cancers that typically affect the kidneys and soft tissues, sometimes occurring in the brain as atypical teratoid rhabdoid tumors (ATRT). The kidney and soft tissue variant, known as malignant rhabdoid tumor (MRT), is most common in infants and toddlers, with an average diagnosis age of 15 months. In the United States, only 35 to 50 new cases of MRT are diagnosed annually. These tumors can spread to other parts of the body. While the exact cause is unknown, research has linked a mutation in the SMARCB1 gene to nearly all rhabdoid tumors. This mutation can sometimes occur in a patient’s normal cells, increasing their risk of developing multiple tumors. Often, the first sign of MRT is an abdominal lump or mass, with some children experiencing urination difficulties or blood in the urine.

About RMS – Rhabdomyosarcoma

Rhabdomyosarcoma is a rare cancerous tumor that develops in the body’s soft tissues, which connect, support, and surround organs and other structures. It originates from rhabdomyoblast cells, which form early in embryonic development, making this cancer more prevalent in children than adults. The tumor commonly appears in the head, neck, bladder, vagina, arms, legs, and trunk, but can also occur in areas with minimal skeletal muscle, such as the prostate, middle ear, or bile duct system. Despite being the most common childhood soft-tissue sarcoma, rhabdomyosarcoma affects only about 250-300 children annually in the United States. There are two primary types of this cancer: embryonal rhabdomyosarcoma (ERMS), which is more common and typically affects children under six, and alveolar rhabdomyosarcoma (ARMS), which accounts for approximately 20 percent of cases and is more frequently found in older children.

About Hepatoblastoma

Hepatoblastomas are the most common primary malignant liver tumors in pediatric patients, typically occurring within the first two years of life. These tumors are classified into two histologic types: epithelial and mixed. While most hepatoblastomas are sporadic, about one-third of cases are associated with genetic conditions such as Beckwith-Weidemann syndrome, familial adenomatous polyposis (FAP), Edward syndrome (trisomy 18), nephroblastoma, and Down syndrome. Infants with low birth weight are at a higher risk of developing hepatoblastoma, and there is evidence linking the tumor to preeclampsia and parental tobacco smoking before and during pregnancy. The most common genetic mutation in hepatoblastoma involves the Wnt signaling pathway, leading to the accumulation of beta-catenin, particularly in sporadic cases. In more aggressive cases, activation of TERT (human telomerase reverse transcriptase) and MYC signaling has been observed. Hepatoblastoma is a rare tumor, accounting for approximately 1% of all pediatric tumors in North America and Europe. However, its incidence is slowly increasing globally, with a slight predominance in males.