On October 17, 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 hematologic malignancies and solid tumors, reported that the South Korean Ministry of Food and Drug Safety (MFDS) has approved a supplemental New Drug Application (sNDA) for XPOVIO (selinexor) in combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma (MM) who have received at least one prior therapy (Press release, Antengene, OCT 17, 2024, View Source [SID1234647251]).

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!

Prior to the recent approval, XPOVIO has been approved for two indications in South Korea that are: in combination with dexamethasone for the treatment of adult patients with relapsed or refractory MM (R/R MM); and as a monotherapy for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL). In July 2024, XPOVIO was included into the reimbursement drug list in South Korea, thus became the first XPO1 inhibitor approved for public insurance coverage in the country.

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 countries and regions in APAC and included in the national insurance schemes in South Korea, the mainland of China, Australia, and Singapore. This recent approval for XPOVIO in South Korea will bring another innovative therapy to the clinical management of MM patients in South Korea, benefiting countless patients and families.

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 October 17, 2024 Medigene AG (Medigene or the "Company", FSE: MDG1, Prime Standard), an oncology platform company focused on the research and development of T cell receptor (TCR)-guided therapies for the treatment of cancer, reported a universal detection system for 3S (specific, sensitive, and safe) recombinant TCRs (rTCRs), UniTope & TraCR, at the American Society of Gene & Cell Therapy (ASGCT) (Free ASGCT Whitepaper) to be held October 16-17, 2024 in Philadelphia, PA in the US (Press release, MediGene, OCT 17, 2024, View Source [SID1234647250]).

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 presented poster "Seamless Integration of a Universal Epitope into Recombinant TCRs for Tagging and Tracking of TCR-T Cells Expressing 3S TCRs" will be made available after the conference on Medigene’s website: View Source

"We incorporate innovative technologies into our End-to-End Platform, including UniTope and TraCR, a universal detection system for any rTCR across multiple modalities. These two tools may ensure precise tracking and verification of recombinant TCRs contributing to safer and more effective dosing strategies in the development and administration of TCR-guided therapies," said Dolores Schendel, CSO at Medigene. "Following the promising data previously presented at this year’s annual ESMO (Free ESMO Whitepaper) meeting for UniTope-modified rTCRs targeting NY-ESO-1/LAGE-1a, we are excited to now share our initial in vitro data for UniTope-modified rTCRs mKRAS G12V. The UniTope tag, when directly integrated, ensures that a unique identifier is always expressed in rTCR sequences. This represents a major improvement over existing techniques for detecting rTCRs in TCR-guided therapies. The use of UniTope and TraCR technologies will significantly enhance our ability to streamline quality control processes and generate highly accurate data for establishing the ideal drug dosage leading to significant cost and time reductions throughout development."

The poster showcased the Company’s newly developed universal TCR tagging and tracking technology, UniTope & TraCR. Through bioinformatic analysis of T cell receptor beta variable sequences, a six-amino-acid peptide, UniTope, was identified, that is absent in natural TCR beta chains and exhibits low immunogenicity. Further, the UniTope sequence allowed each rTCR to be tagged, adaptable for multi-parameter flow cytometry and ideal for standardized tracking and enrichment of rTCR-T cells with a design that’s easy to implement in complex gene transfer systems. Alongside this, an antibody (TraCR) was also designed to specifically recognize and bind to this unique peptide sequence, enabling precise tracking of the tagged TCRs.

In vitro data demonstrated that insertion of the UniTope tag to rTCR-T cells targeting mKRAS G12V did not alter the expression or functionality of the rTCR. The tagged rTCRs maintained their normal biological activity, indicating that UniTope integration has no negative impact on functionality of the rTCR.

Additionally, safety assessments verified that UniTope-modified rTCRs exhibited the same high safety profile as their unmodified counterparts. These modified rTCRs did not show any unintended recognition or cytotoxic activity against 16 different types of healthy cells tested, ensuring that addition of the UniTope tag does not compromise safety.

Finally, UniTope-modified rTCRs demonstrated equivalent specificity, sensitivity, and safety characteristics compared to unmodified rTCRs. making them highly versatile for use across various therapeutic modalities, including T cell receptor engineered T cell therapies, TCR-guided T cell engagers, and TCR-NK cell therapies.

On October 17, 2024 Xenetic Biosciences, Inc. (NASDAQ:XBIO) ("Xenetic" or the "Company"), a biopharmaceutical company focused on advancing innovative immuno-oncology technologies addressing hard to treat oncology indications, reported it has entered into a Materials Transfer Agreement with Tokyo Medical University to advance the development of its systemic DNase program (Press release, Xenetic Biosciences, OCT 17, 2024, View Source [SID1234647249]).

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!

Under the terms of the agreement, Professor Takuro Nakamura of the Department of Experimental Pathology, Institute of Medical Science at Tokyo Medical University will lead the research program evaluating the effects of human recombinant DNase I (rhDNase I) when given in combination with chemotherapy in a proprietary immunocompetent preclinical mouse model of Ewing sarcoma. Professor Takuro Nakamura’s proprietary immunocompetent Ewing sarcoma model encompasses the biological characteristics, morphology and gene expression profiles of human Ewing sarcoma and has demonstrated translational relevance.

Ewing sarcoma is an aggressive orphan pediatric cancer that grows in bones or soft tissues, accounting for between 2 to 3 percent of all childhood cancers. There is a lack of effective treatment options for children with recurrent and metastatic disease where the five-year survival rate is only 20 to 30 percent for patients that have relapsed.

Clinical studies conducted at Tel Aviv Medical Center between 2010 and 2021 [1] showed that the formation of neutrophil extracellular traps (NETs) in the tumor microenvironment of Ewing sarcoma is an independent prognostic factor, with a clear association between NETs burden and poor prognosis. According to research from these clinical studies, elevated levels of NETs at diagnosis predicted a poor response to neoadjuvant chemotherapy, relapse, and death from the disease.

Xenetic’s proprietary recombinant DNase I is an enzyme that digests NETs in tumor microenvironment. The preclinical studies are designed to evaluate the efficacy of DNase to reduce NETs burden and to increase the efficacy of chemotherapy given in an adjuvant setting.

James Parslow, Interim Chief Executive Officer and Chief Financial Officer of the Company stated, "As part of our overall development strategy, we aim to leverage relationships like the one established with Tokyo Medical University. Our commitment to the DNase program remains steadfast, and we are pleased to enter into this agreement to further expand our growing body of data."

About DNase-Based Oncology Platform

Xenetic’s DNase-based oncology platform is designed to target NETs, which are weblike structures composed of extracellular chromatin coated with histones and other proteins. In cancer, NETs are expelled by activated neutrophils into the tumor microenvironment and blood, thereby promoting cancer spread and local and systemic immunosuppression. Reduction of NETs burden via application of Xenetic’s proprietary recombinant human DNase I has been shown to improve efficacy of immunotherapy, adoptive cell therapy and chemotherapy in preclinical animal models.

On October 17, 2024 TuHURA Biosciences, Inc. (NASDAQ:HURA) ("TuHURA" or the "Company"), a Phase 3 registration-stage immune-oncology company developing novel technologies to overcome resistance to cancer immunotherapy reported the completion of its previously announced merger with Kintara Therapeutics, Inc. (now TuHURA Biosciences, Inc.) (Press release, TuHURA Biosciences, OCT 17, 2024, View Source [SID1234647248]). The combined company will operate under the name "TuHURA Biosciences, Inc." and will focus on advancing TuHURA’s innate immune response agonists and tumor microenvironment modulators, two technologies that seek to overcome the major obstacles that limit the effectiveness of current immunotherapies in treating cancer. The Company is preparing to initiate a single Phase 3 accelerated approval registration trial in the first half of 2025 for treatment of 1st line Merkel Cell carcinoma under SPA agreement with FDA.

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 shares of the Company’s common stock, previously trading under the ticker symbol "KTRA," will commence trading on a post-reverse split and post-business combination basis, on The Nasdaq Capital Market under the ticker symbol "HURA", effective October 18, 2024. The Company’s common stock is now represented by a new CUSIP number, 898920103.

As a result of the merger, post-merger Kintara equityholders collectively own approximately 2.85% (or approximately 5.45% after giving effect to the shares issued pursuant to the CVR Agreement if the milestones are achieved) of the common stock of the combined company on a pro forma fully diluted basis. TuHURA equityholders collectively own approximately 97.15% (or approximately 94.55% after giving effect to the shares issued pursuant to the CVR Agreement if the milestones are achieved) of the common stock of the combined company on a pro forma fully diluted basis.

"This marks a transformational milestone for both companies and is a significant step in the evolution of TuHURA. As we look to the future, which I believe has never been brighter, we are working to solve a significant issue with current cancer immunotherapies," commented Dr. James Bianco, President and Chief Executive Officer of TuHURA. "Our novel technologies are designed to overcome resistance to cancer immunotherapy, and we are planning to initiate a single Phase 3 accelerated approval registration trial in the first half of 2025 with our lead innate immune response agonist, IFx-2.0. If successful, not only does it provide the ability to target additional oncology indications but also unlocks tremendous value for all stakeholders."

Advancing Novel Technologies to Overcome Resistance to Cancer Immunotherapy

TuHURA is a Phase 3 registration-stage immuno-oncology company developing novel technologies to overcome primary and acquired resistance — two major obstacles to cancer immunotherapy’s ability to treat and cure cancer.

Immune Fx (IFx) Innate Immune Response Agonists: TuHURA’s IFx technology utilizes a proprietary plasmid DNA ("pDNA") or messenger RNA ("mRNA") which, when introduced into or targeted to a tumor cell, results in the expression of a highly immunogenic bacterial protein (Emm55) on the surface of the tumor cell. TuHURA’s lead innate immune response agonist candidate, IFx-2.0, is designed to overcome primary resistance to checkpoint inhibitors. TuHURA is preparing to initiate a single Phase 3 accelerated approval registration trial of IFx-2.0 administered as an adjunctive therapy to Keytruda (pembrolizumab) in first line treatment for advanced or metastatic Merkel Cell Carcinoma under a SPA agreement with the US FDA, in the first half of2025.

Tumor Microenvironment Modulators: Leveraging its Delta receptor technology, TuHURA is developing bi-specific immune modulating Antibody (ADC) or Peptide (PDC) Drug Conjugates targeting Myeloid Derived Suppressor Cells to inhibit their immune suppressing effects on the tumor microenvironment to prevent T cell exhaustion and acquired resistance to checkpoint inhibitors and cellular therapies.

About the Transaction

Under the terms of the merger agreement, Kayak Mergeco, Inc., Kintara’s wholly-owned subsidiary, will merge with and into the private-company TuHURA, with TuHURA surviving the merger and becoming the combined company’s direct, wholly-owned subsidiary effective at 12:03 AM Eastern Time on October 18, 2024.

As previously announced, in connection with the merger and pursuant to the Contingent Value Rights Agreement (the "CVR Agreement"), the Company will issue CVRs to legacy Kintara stockholders (or in the case of warrants to purchase shares of Kintara common stock, each share of Kintara common stock for which such warrant to purchase shares of Kintara stock is exercisable), entitling such holders to an aggregate of approximately 1,539,918 shares of the combined company’s common stock on a post-split basis, upon the achievement of certain milestones as set forth in the CVR Agreement.

The combined company will be led by James Bianco as President and Chief Executive Officer of TuHURA. In addition to Mr. Bianco, the TuHURA leadership team includes current members of management Dan Dearborn as Chief Financial Officer and Dennis Yamashita as Chief Scientific Officer.

The Board of Directors of TuHURA will be composed of James Bianco, James Manuso, Alan List, George Ng and Robert Hoffman.

Advisors

Lucid Capital Markets, LLC acted as the exclusive financial advisor and Lowenstein Sandler LLP acted as legal counsel to Kintara. H.C. Wainwright & Co. acted as the exclusive financial advisor and Foley & Lardner LLP acted as legal counsel to TuHURA.

On October 17, 2024 Nusano, a physics company transforming the production of radioisotopes, and Starget Pharma, a clinical-stage biotechnology company developing precision peptide radioligand therapies focused on difficult to treat cancers, reported a supply agreement to advance the development of Starget’s Smart Targeted Radioligands (STRs) (Press release, Nusano, OCT 17, 2024, View Source [SID1234647247]). The supply agreement is expected to support Starget’s STR isotope needs from discovery through commercialization and will include both common radioisotopes as well as rare alpha particle-emitters such as Astatine-211, Lead-212, and Actinium-225.

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!

"We are excited to partner with Nusano, a leader in radioisotope production, to support the development of our novel pipeline of smart targeted radioligands," said Sigal Kalmanson Cusnir, CEO of Starget Pharma. "Our STR platform technology enables the rapid design and evaluation of radiotherapies in an isotope-agnostic manner, allowing us to optimize performance by tumor type. We are focused now on advancing our clinical pipeline, beginning with the planned initiation of a Phase 1b clinical trial in early 2025. The Nusano agreement will ensure that we have a reliable radioisotope supply chain, facilitating near and long term growth, with the ultimate goal of radically improving patient care and outcomes."

Starget’s STR platform is advancing the field of molecular radiation using its proprietary backbone cyclization technology to create innovative and diversified peptide radioligand candidates with enhanced properties. These STRs are designed to bind and deliver a payload of radiation specifically to biological targets that are overexpressed in cancer compared to normal cells. This highly focused radiation then damages the DNA in the cancer cells, leading to selective cell death and tumor shrinkage. Due to their unique molecular interaction with the target, STRs act with high sensitivity and precision, enabling effective radiation targeting tumors and metastasis.

Radioisotopes are essential components in the active pharmaceutical ingredients (API) used in new and emerging cancer therapies including molecular radiation. Existing supply chains for these treatment-enabling resources are often strained, posing a risk to patient care, clinical trials, and ongoing drug development.

Nusano is working to stabilize supply chains and enable innovation by bringing new sources of radioisotopes to medical and industrial markets. Opening in 2025 in West Valley City, Utah, the Nusano production platform will be capable of generating more than 25 radioisotopes applicable to medical and industrial uses. It is anchored by a proprietary ion source technology which accelerates heavy particles (alphas and deuterons) to generate high volume, high quality (cGMP-grade) radioisotopes with unparalleled efficiency using eco-friendly methods. The result is one of the first significant advancements in radioisotope production in decades.

Chris Lowe, CEO of Nusano commented, "The Nusano platform will make medical radioisotopes available in varieties and volumes needed to broaden and accelerate radiotherapeutics development. We share Starget’s enthusiasm for finding the right isotope to target specific tumor types and look forward to working with them to advance more isotopes into clinical development for the betterment of cancer patients around the world."