On December 3, 2024 Duality Biologics ("DualityBio"), a clinical-stage biotech company focusing on the discovery and development of next-generation antibody-drug conjugate (ADC) therapeutics, reported that it has entered into an exclusive option agreement with GSK for a potentially best-in-class ADC candidate, DB-1324 (Press release, DualityBio, DEC 3, 2024, View Source [SID1234648769]). Under the agreement, DualityBio will grant GSK an exclusive option to obtain a license to develop and commercialize DB-1324 worldwide (excluding mainland China, Hong Kong, and Macau) (the "Option").

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!

DB-1324 is an ADC candidate built with DualityBio’s proprietary and clinically validated Duality Immune Toxin Antibody Conjugate (DITAC) platform. The molecule, currently in preclinical development, leverages DualityBio’s DITAC platform against a gastrointestinal (GI) cancer target. There is high unmet medical need for patients with GI cancer as it represents 35% of all cancer-related deaths and approximately 26% of the global cancer incidence.[1] This ADC molecule has the potential to unlock multiple combination therapy opportunities to strategically complement GSK’s oncology portfolio.

Under the terms of the agreement, GSK will pay $30 million upfront and additional pre-option milestone payments to obtain an exclusive option for exclusive worldwide rights for DualityBio’s ADC (excluding China’s mainland, Hong Kong, and Macau). Upon GSK exercising the Option, DualityBio will receive an option exercise fee as well as potential development, regulatory and commercial milestone payments totalling up to $975 million. Upon commercialisation, GSK will pay tiered royalties on DB-1324’s global net sales outside mainland China, Hong Kong, and Macau. GSK will receive royalties on net sales in mainland China, Hong Kong and Macau.

Hesham Abdullah, SVP, Global Head Oncology, R&D, GSK, said: "GSK has built a portfolio of novel antibody-drug conjugates underpinned by our deep expertise in tumour cell-targeting mechanisms. Given the unique ability of ADCs to address certain targets on tumour cells while sparing healthy ones, we are confident in our strategic focus on this modality as it could advance new therapeutic treatments for the most challenging tumour types."

John Zhu, Chief Executive Officer of Duality Biologics, said: "DualityBio is dedicated to becoming a leading global next-generation ADC company. We are very glad to have entered into this agreement with GSK. Through this collaboration, we will work together to advance our innovative ADC program in gastrointestinal cancer to address unmet medical needs. DualityBio’s unique and validated ADC technology platform can continue to empower more partners around the world and provide innovative treatment options for global patients."

On December 3, 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 USD $1 million milestonepayment from Regeneron Pharmaceuticals, Inc. was triggered (Press release, MediGene, DEC 3, 2024, View Source [SID1234648766]). Regeneron purchased the MAGE-A4-TCR program as part of its acquisition of2seventy bio Inc.’s pre-clinical and clinical oncology and autoimmune cell therapy pipeline, which closed in April 2024. The payment was triggered by a development milestone for a trial in China led by JW Therapeutics (also a prior collaborator of 2seventy bio, Inc.) of Regeneron’s MAGE-A4 cell therapy, which contains a Medigene generated T cell receptor (TCR) targeting MAGE-A4.

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 that this program is moving forward, incorporating our TCR directed at MAGE-A4 into the clinic and potentially providing the first clinical validation of our unique TCR discovery and generation capabilities and our End-to-End Platform technologies," said Dr. Selwyn Ho, Chief Executive Officer of Medigene. "We look forward to the results of this trial and remain committed to delivering best-in-class, differentiated T cell receptors for use in multiple TCR-guided therapies for patients with solid tumors."

This payment has been included in the current financial guidance provided by the Company, and therefore confirmation of this milestone does not change 2024 guidance.

On December 3, 2024 Gilead Sciences, Inc. (Nasdaq: GILD) and Tubulis reported that they have entered into an exclusive option and license agreement to discover and develop an antibody-drug conjugate (ADC) against a solid tumor target (Press release, Gilead Sciences, DEC 3, 2024, View Source [SID1234648765]).

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!

Through this agreement, Gilead will gain access to Tubulis’ proprietary Tubutecan and Alco5 platforms. The companies will collaborate to select the best technology to utilize, with Tubulis leading discovery and development efforts to design a topoisomerase I inhibitor-based ADC candidate with superior biophysical properties and stability to address current treatment challenges such as durability and off-target toxicity.

"As we expand our oncology portfolio to address the greatest gaps in care, accessing novel technologies is critical to advancing our pipeline," said Flavius Martin, MD, Executive Vice President, Research, Gilead Sciences. "With Gilead’s ongoing focus on innovating with next-generation therapies and combinations, we are excited to partner with Tubulis to explore a range of solutions that may help increase the therapeutic value of the ADC modality."

"Gilead has established a long track record of developing drugs that provide a significant step-up in therapeutic value, making them a great collaborator for leveraging our technology platforms, in line with our vision of fundamentally changing the ADC landscape," said Dominik Schumacher, PhD, CEO and co-founder of Tubulis. "Tubulis remains primarily focused on driving value through our own clinical development programs while selectively building partnerships with leaders in the industry."

Terms of the Agreement

Under the terms of the agreement, Tubulis will receive an upfront payment of $20 million and, if Gilead exercises its option, a separate option exercise fee of $30 million. In addition, Tubulis will be eligible for development and commercialization milestone payments totaling up to $415 million, plus mid-single to low double-digit tiered royalties on sales of marketed products resulting from the collaboration. Tubulis will lead early-stage research and development activities for the ADC program. If Gilead exercises its option to exclusively license the program, Gilead will be responsible for further development and commercialization activities for all products resulting from the collaboration.

Gilead does not exclude acquired IPR&D expenses from its non-GAAP financial measures. This transaction with Tubulis is expected to reduce Gilead’s GAAP and non-GAAP 2024 EPS by approximately $0.01.

On December 3, 2024 Rezolute, Inc. (Nasdaq: RZLT) ("Rezolute" or the "Company"), a late-stage biopharmaceutical company dedicated to developing transformative therapies for rare diseases with serious unmet needs, reported the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to ersodetug for the treatment of hypoglycemia due to tumor HI (Press release, Rezolute, DEC 3, 2024, View Source [SID1234648764]).

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!

"FDA’s granting of Orphan Drug Designation is a recognition of the serious unmet need patients with tumor hyperinsulinism face and validates the potential significant benefit that ersodetug can provide," said Susan Stewart, J.D, Chief Regulatory Officer of Rezolute. "Tumor HI requires directed treatments for hypoglycemia to prevent serious adverse outcomes and improve patients’ quality of life, as well as to enable patients to continue cancer treatments. We are thrilled with FDA’s designation, which allows us to continue developing a potential universal treatment for hypoglycemia caused by all forms of HI."

The FDA’s Orphan Drug Designation is intended to encourage the development of treatments for rare diseases. Orphan Drug Designation offers benefits including seven years of market exclusivity protection and may shorten the clinical development path through potential qualification for expedited pathways to approval.

About Tumor Hyperinsulinism (HI)

Tumor HI is a rare disease that may be caused by two distinct types of tumors: islet cell tumors (ICTs) and non-islet cell tumors (NICTs), both of which lead to hypoglycemia as a result of excessive activation of the insulin receptor. Insulinomas are the most common type of ICT and may cause hypoglycemia by stimulating the over production of insulin. A variety of different NICTs, particularly hepatocellular carcinoma, can cause hypoglycemia by producing and secreting insulin-like paraneoplastic substances such as IGF-2 that bind to and activate the insulin receptor. With high morbidity and mortality rates within tumor HI, there remains a significant unmet need for new therapies directed at hypoglycemia treatment. Ersodetug has shown real-world benefit in patients with insulinoma and preclinical studies have shown that ersodetug can similarly blunt IGF-2 and insulin-mediated insulin-receptor signaling.

About Ersodetug

Ersodetug is a fully human monoclonal antibody that binds to a unique allosteric site on insulin receptors to counteract the effects of insulin receptor over-activation by insulin and related substances (such as IGF-2), thereby improving hypoglycemia in the setting of hyperinsulinism (HI). Because ersodetug acts downstream from the pancreas, it has the potential to be universally effective at treating hypoglycemia due to any form of HI.

On December 3, 2024 Beyond Cancer, Ltd., a clinical-stage biotechnology company developing ultra-high concentration nitric oxide (UNO) as an immunotherapeutic for solid tumors, reported that the Israeli Ministry of Health (IMOH) has approved the use of Low Volume UNO (LV UNO) in a Phase 1b clinical trial of LV UNO in combination with anti-PD-1 therapy (Press release, Beyond Cancer, DEC 3, 2024, View Source [SID1234648763]). The trial will be conducted at four sites in Israel and patient screening will begin in the first quarter of 2025.

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 1b trial (NCT05351502) is a clinical proof-of-concept trial that will assess the intratumoral administration of LV UNO in patients with unresectable cutaneous or subcutaneous histologically confirmed primary or metastatic lesions, who have shown disease progression or prolonged stable disease ( 12 weeks) after receiving a single agent anti-PD-1 containing treatment. The trial, which is expected to enroll up to 20 subjects, is designed to assess the preliminary efficacy of LV UNO by objective response rate (ORR) and duration of response (DOR) per RECIST v1.1 and secondarily immune-related response via iRECIST. Safety and tolerability of LV UNO in combination with anti-PD-1 therapy, as well as its potential to enhance the type, density, and distribution of immune cells within the tumor microenvironment will also be observed. Topline data from the Phase 1b portion of the study are anticipated in the second half of 2025.

"We are excited to initiate the Phase 1b trial of LV UNO, a potentially groundbreaking solid tumor treatment approach, in combination with PD-1 inhibitors," said Dr. Jedidiah Monson, Chief Medical Officer of Beyond Cancer. "In preclinical studies, a single dose of UNO has been shown to increase PD-L1 expression and improve overall survival in animal models compared to anti-PD-1 alone. Further, Phase 1a human data that demonstrated immune system activation were presented at ASCO (Free ASCO Whitepaper)’s Key Opinion Leader Event held in June 2024. We look forward to the Phase 1b trial results to establish the basis of further investigation of UNO in combination with PD-1 inhibitors."

"The initiation of the Phase 1b trial represents a major step forward in our vision for personalized cancer treatment. We see UNO as a complementary therapy for future cancer treatment paradigms, particularly for patients with anti-PD-1 refractory or resistant disease, potentially offering more patients access to effective treatment," stated Dr. Selena Chaisson, Chief Executive Officer, and Director of Beyond Cancer.

About Nitric Oxide

Nitric Oxide (NO) is a potent molecule, naturally synthesized in the human body, proven to play a critical role in a broad array of biological functions. In the airways, NO targets the vascular smooth muscle cells that surround the small resistance arteries in the lungs. Currently, exogenous inhaled NO is used in adult respiratory distress syndrome, post certain cardiac surgeries and persistent pulmonary hypertension of the newborn to treat hypoxemia. Additionally, NO is believed to play a key role in the innate immune system and in vitro studies suggest that NO possesses anti-microbial activity not only against common bacteria, including both gram-positive and gram-negative, but also against other diverse pathogens.

About UNO Therapy for Solid Tumors

Cancer is the second leading cause of death globally, with tumor metastases responsible for approximately 90% of all cancer-related deaths. Current cancer treatment modalities generally include chemotherapy, immunotherapy, radiation, and/or surgery. Ultra-high concentration Nitric Oxide (UNO) therapy is a completely new approach to preventing relapse or metastatic disease. In vitro murine data show that local tumor ablation with UNO stimulates an anti-tumor immune response in solid tumor cancer models. Beyond Cancer, Ltd. believes that UNO has the potential to prevent relapse or metastatic disease with as little as a single 5-minute treatment and with limited toxicity or off-target effects.