On January 30, 2025 Owkin, the first end-to-end AI-biotech that uses agentic AI to revolutionize drug discovery, development, and diagnostics, reported that the first patient has been dosed in its Phase I clinical trial of OKN4395 on January 22, 2025 (Press release, Owkin, JAN 30, 2025, View Source [SID1234649973]). OKN4395 builds upon well-characterized EP2/EP4 inhibition, through a newly identified and equipotent inhibition of DP1. The clinical significance of this first-in-class triple inhibition is being evaluated in this trial.

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!

AI-optimized study design

Owkin’s proprietary K1.0 Operating System was instrumental in advancing OKN4395 from asset selection through to clinical development. By building a detailed biological understanding of the EP2/EP4/DP1 targets and their complex mechanisms of action, Owkin’s AI operating system was used to optimize the clinical development strategy. The program integrates Owkin’s expertise in AI-driven indication selection, external control arms (digital twins) for early anti-tumor activity insights in Phase I, and biomarker-led patient subtyping to enhance the probability of clinical success.

Thomas Clozel, MD, CEO & Co-founder of Owkin, said: "OKN4395 reflects not only a decade of discovery efforts by Idorsia and its collaborators but also exemplifies the transformative power of Owkin’s K1.0 Operating System. This milestone underscores our ability to rapidly translate a promising asset into an AI-optimized clinical program."

A first-in-class asset: OKN4395

Prostaglandins E2 and D2 (or PGE2, PGD2) are hormone-like molecules produced naturally in the body, and are the natural ligands for prostanoid receptors EP2, EP4, and DP1, respectively. The PGE2/EP2/EP4 and PGD2/DP1 pathways are both known to be immunosuppressive1,2. Well-described in oncology, hyperactivity of the PGE2/EP2/EP4 pathway in certain cancers allows them to avoid the immune system’s effector mechanisms, leading to progression and resistance through tumor growth or metastasis1.

OKN4395 is the first compound in the clinic to selectively inhibit EP2, EP4, and DP1 receptors. This novel mechanism offers the potential to restore immune function, providing transformative treatment options for patients with advanced solid tumors.

The INVOKE Study (OKN-4395-121)

INVOKE is a global, multicenter, Phase Ia/1b, first-in-human, open-label trial evaluating OKN4395 in patients with advanced solid tumors. Phase Ia primarily assesses safety and tolerability through dose escalation of OKN4395 as both a monotherapy and in combination with pembrolizumab. Phase Ib will expand into a further four cohorts, and assess preliminary anti-tumor activity, as well as safety and extensive exploratory analyses.

On January 30, 2025 Orion Corporation ("Orion"), a globally operating pharmaceutical company, and Invenra Inc., an innovative biotechnology company with proprietary technologies for discovering novel therapeutics, reported that they have entered into a research collaboration to discover bispecific antibodies using Invenra’s B-Body platform (Press release, Orion, JAN 30, 2025, View Source [SID1234649972]).

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 agreements, Invenra will leverage its B-Body bispecific antibody platform from monoclonal antibody discovery to optimized panels of bispecific leads. Orion will be responsible for the selection of targets and will be solely responsible for the development, manufacturing, and global commercialization of these candidates. The agreement provides Orion with commercial licenses for up to two bispecific antibodies.

"This collaboration highlights the strength and versatility of our B-Body platform in addressing complex biological challenges," said Roland Green, CEO of Invenra. "We are thrilled to work with Orion, a company that shares our commitment to delivering innovative therapies that address critical unmet medical needs."

"Partnering with Invenra represents an important step in Orion’s strategy to expand our portfolio in the bispecific antibody space," said Antti Haapalinna, Vice President, Head of External Science & Partnering R&D, Orion. "Invenra’s cutting-edge bispecific discovery platform, combined with Orion’s expertise in development and commercialization, will accelerate the creation of impactful new therapies for patients worldwide."

This discovery collaboration combines Invenra’s advanced engineering expertise in bispecific antibody discovery with Orion’s established track record in pharmaceutical innovation, setting the stage for the development of next-generation therapeutic solutions.

On January 30, 2025 Astrazeneca reported that the first patient has been dosed in the TROPION-Lung12 phase 3 trial evaluating the efficacy and safety of adjuvant DATROWAY (datopotamab deruxtecan) plus rilvegostomig or rilvegostomig monotherapy versus standard of care in patients with stage 1 adenocarcinoma non-small cell lung cancer (NSCLC) after complete surgical resection who are ctDNA-positive or have other high risk pathological features (Press release, AstraZeneca, JAN 30, 2025, View Source [SID1234649971]).

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!

DATROWAY is a specifically engineered TROP2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca (LSE/STO/Nasdaq: AZN).

Standard treatment for stage 1 NSCLC is tumor resection, but up to 40% of patients may experience disease recurrence.1,2,3 Tumor resection is typically followed by observation but adjuvant chemotherapy and/or immunotherapy may be offered to patients with stage 1b disease who are identified to be at high risk of relapse.4 However, novel strategies to identify high risk patients are needed as well as additional treatment options in the adjuvant setting. Research suggests that ctDNA screening may help identify high risk patients who are most likely to benefit from adjuvant therapy.5,6

"After surgery for early-stage non-small cell lung cancer, there is no established consensus on adjuvant therapy. As a result, patients may either undergo observation or receive adjuvant chemotherapy and/or immunotherapy if they have stage 1b disease and are determined to be at high risk for disease recurrence," said Mark Rutstein, MD, Global Head, Oncology Clinical Development, Daiichi Sankyo. "The TROPION-Lung12 trial will help us better understand the role of DATROWAY in combination with immunotherapy in the adjuvant setting as a potential treatment regimen to help prevent disease recurrence in patients with high risk stage 1 adenocarcinoma following surgery."

"With TROPION-Lung12, we are simultaneously deploying a novel strategy for identifying patients with lung cancer who are at an increased risk of disease recurrence after surgery and evaluating novel treatment options in the adjuvant setting, including rilvegostomig with and without DATROWAY," said Cristian Massacesi, MD, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca. "The ambitious approach in this trial underscores our commitment to both enabling more personalized treatment decisions and delivering innovative treatment options to patients with cancer."

About TROPION-Lung12
TROPION-Lung12 is a global, multicenter, three-arm, open-label phase 3 trial where patients will be randomized in a 2:1:2 ratio to evaluate the efficacy and safety of adjuvant DATROWAY (6 mg/kg) in combination with rilvegostomig (750 mg) or rilvegostomig (750 mg) monotherapy versus observation or standard of care adjuvant chemotherapy regimens in those with stage 1 (stage 1a or 1b with tumors < 4 cm) adenocarcinoma NSCLC who are ctDNA-positive (as determined by an investigational ctDNA assay) or have high risk pathological features (as determined by central pathology assessment).

The primary endpoint of TROPION-Lung12 is disease-free survival following complete tumor resection as assessed by blinded independent central review in patients treated with adjuvant DATROWAY and rilvegostomig versus those who undergo observation or receive standard of care. Key secondary endpoints include patient-reported physical functions, patient-reported quality of life outcomes, overall survival and safety.

TROPION-Lung12 will enroll approximately 660 patients in Asia, Europe, North America and South America. For more information visit ClinicalTrials.gov.

Rilvegostomig is AstraZeneca’s PD-1/TIGIT bispecific antibody. The TIGIT component of rilvegostomig is derived from the clinical-stage anti-TIGIT antibody, COM902, developed by Compugen Ltd. (Nasdaq/TASE: CGEN).

About Non-Small Cell Lung Cancer
Nearly 2.5 million lung cancer cases were diagnosed globally in 2022.7 NSCLC is the most common type of lung cancer and adenocarcinoma is the most common subtype of NSCLC, accounting for about 40% of all lung cancer cases.8

For patients with stage 1 NSCLC, standard treatment is tumor resection and observation.4 For patients with stage 1b disease or those otherwise identified as having a high risk of relapse based on clinical or pathological features, tumor resection may be followed by adjuvant chemotherapy and/or immunotherapy.4 However, strategies to identify high risk patients are needed as well as more durable and effective treatment options in the adjuvant setting. Research suggests that screening for ctDNA in patients with stage 1 NSCLC may help identify patients most likely to benefit from adjuvant therapy and that combining an immunotherapy with an ADC has the potential to drive deeper and more durable tumor responses.5,6

TROP2 is a protein broadly expressed in the majority of NSCLC tumors.9 There is currently no TROP2 directed ADC approved for the treatment of lung cancer.10,11

About DATROWAY
DATROWAY (datopotamab deruxtecan; datopotamab deruxtecan-dlnk in the U.S. only) is a TROP2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, DATROWAY is one of six DXd ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programs in AstraZeneca’s ADC scientific platform. DATROWAY is comprised of a humanized 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.

DATROWAY (6 mg/kg) is approved in Japan and the U.S. for the treatment of adult patients with unresectable or metastatic HR positive, HER2 negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease based on the results from the TROPION-Breast01 trial.

About the DATROWAY Clinical Development Program
A comprehensive global clinical development program is underway with more than 20 trials evaluating the efficacy and safety of DATROWAY across multiple cancers, including NSCLC, triple negative breast cancer and HR positive, HER2 negative breast cancer. The program includes eight phase 3 trials in lung cancer and five phase 3 trials in breast cancer evaluating DATROWAY as a monotherapy and in combination with other anticancer treatments in various settings.

On January 30, 2025 Tubulis reported that its second drug candidate, TUB-030, has entered clinical evaluation with successful dosing of the first patient in the 5-STAR 1-01 Phase I/IIa trial (NCT06657222). The study is evaluating TUB-030, Tubulis’ next-generation antibody-drug conjugate (ADC), in patients with advanced solid tumors (Press release, Tubulis, JAN 30, 2025, View Source [SID1234649970]). The ADC targets 5T4, an oncofetal antigen expressed in a broad range of solid tumors. The program was developed using Tubulis’ proprietary Tubutecan linker-payload platform, which enables superior biophysical properties for precise and sustained on-tumor payload delivery.

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!

"This milestone for TUB-030 demonstrates our ability to execute on our strategy to advance innovative programs into our proprietary pipeline and rapidly bring them into the clinic," said Dominik Schumacher, PhD, Chief Executive Officer and Co-founder of Tubulis. "As an organization, Tubulis has made a large step forward with two differentiated ADC molecules in clinical evaluation in less than a year. Our goal is to continue being an innovation driver in the field by delivering on the transformative potential of our platforms for patients."

The multicenter, first-in-human, dose escalation and optimization Phase I/IIa study 5-STAR 1-01 aims to investigate the safety, tolerability, pharmacokinetics, and efficacy of TUB-030 as a monotherapy to treat a broad range of solid tumors. The trial will enroll a total of 130 patients and will be conducted at sites across the US and Canada. Phase I comprises dose escalation to determine the safety profile and to identify the maximum tolerated dose and/or the identified dose for optimization in patients with advanced solid tumor indications. Phase IIa will focus on dose optimization, safety, and preliminary efficacy of TUB-030 in selected indications.

"Building on our strong preclinical efficacy and safety data, we are expecting that targeting 5T4 with our high-performance ADC technology may offer a new precision therapy option for a variety of solid tumor indications. With our differentiated target, a strong bystander effect and efficient and durable target engagement via the Tubutecan platform, TUB-030 provides the potential to induce robust anti-tumor activity in 5T4-expressing tumors," stated Günter Fingerle-Rowson, MD, PhD, Chief Medical Officer at Tubulis.

TUB-030 consists of a humanized, Fc-silenced IgG1 antibody targeting 5T4 equipped with Tubulis’ proprietary Tubutecan technology, which is based on P5 conjugation chemistry and the topoisomerase-1 inhibitor exatecan. Tubulis previously presented a comprehensive preclinical data set at AACR (Free AACR Whitepaper) demonstrating TUB-030’s stability and minimal loss of linker-payload conjugation. In a range of preclinical models, TUB-030 produced high and long-lasting anti-tumor responses, including responses at relatively low 5T4 expression levels, while maintaining an excellent safety and tolerability profile. A single treatment with TUB-030 eliminated tumors in a triple-negative breast cancer mouse model, further underlining its potential efficacy. Preclinical analysis including safety, efficacy and pharmacokinetics demonstrated that TUB-030 has a therapeutic window in a large variety of solid tumors.

About TUB-030 and the Tubutecan Technology

Tubulis’ second antibody-drug conjugate (ADC) TUB-030 is directed against 5T4, an oncofetal antigen, expressed in a broad range of solid tumor types. It consists of an IgG1 antibody targeting 5T4 connected to the Topoisomerase I inhibitor exatecan through a cleavable linker system based on the company’s proprietary P5 conjugation technology with a homogeneous DAR of 8. P5 conjugation is a novel chemistry for cysteine-selective conjugation that enables ADC generation with unprecedented linker stability and biophysical properties. The candidate is currently being investigated in a multicenter Phase I/IIa study (5-STAR 1-01, NCT06657222) that aims to evaluate the safety, tolerability, pharmacokinetics, and efficacy of TUB-030 as a monotherapy in advanced solid tumors.

On January 30, 2025 enGene Holdings Inc. (Nasdaq: ENGN, or "enGene" or the "Company"), a clinical-stage genetic medicines company whose non-viral lead investigational product detalimogene voraplasmid (also known as detalimogene, and previously EG-70) is in an ongoing pivotal study in patients with high-risk, Bacillus Calmette-Guérin (BCG)-unresponsive, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS), reported three poster presentations at the 2025 ASCO (Free ASCO Whitepaper) Genitourinary Cancers Symposium (ASCO GU) to be held February 13-15, 2025 in San Francisco (Press release, enGene, JAN 30, 2025, View Source [SID1234649969]).

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!

"Patients with NMIBC often face a debilitating, multi-year journey with limited treatment options and significant negative impacts to daily life. These patients are most commonly treated by community urologists who face unique challenges accessing and providing optimal care, including global treatment shortages and complex usage and handling," said Ron Cooper, Chief Executive Officer of enGene. "We are determined to develop genetic therapies for underserved conditions like NMIBC and ultimately provide a long overdue treatment innovation designed to advance care and ease the treatment burden."

There are an estimated 730,000 patients in the U.S. living with bladder cancer, and approximately 75% to 80% of all bladder cancer diagnoses are NMIBC. Among patients diagnosed with high-risk NMIBC, more than half (50-70%) will become BCG-unresponsive and experience recurrence and/or progression after treatment.

"The current treatment options for patients with high-risk NMIBC are sadly sub-optimal, often resulting in disease progression, recurrence or removal of the bladder as a life-altering measure of last resort," said Anthony Cheung, Chief Scientific Officer and Co-Founder of enGene. "If approved, we believe detalimogene voraplasmid will be uniquely compelling to both patients and physicians by combining a streamlined administration process designed to ease the treatment experience with durable efficacy and a favorable safety and tolerability profile."

Presentation details are outlined below:

Preliminary results from LEGEND: A phase 2 study of detalimogene voraplasmid (EG-70), a novel, non-viral intravesical gene therapy for patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS)

Abstract #: 802
Poster #: F29
Clinical Trial Registration Number: NCT04752722
Session Title: Poster Session B: Urothelial Carcinoma
Presentation Date/Time: Friday, February 14 from 11:30am-12:45pm PT
Location: Level 1, West Hall
Presenting Author: John Taylor III, MD, MS, Professor of Urology & Cancer Biology, University of Kansas Cancer Center
Mechanism of action and translation to the clinic of detalimogene voraplasmid (EG-70): A novel, investigational, non-viral immunotherapy for non-muscle-invasive bladder cancer (NMIBC)

Abstract #: 826
Poster #: G22
Clinical Trial Registration Number: NCT04752722
Session Title: Poster Session B: Urothelial Carcinoma
Presentation Date/Time: Friday, February 14 from 11:30am-12:45pm PT
Location: Level 1, West Hall
Presenting Author: Vikram Narayan, MD, Assistant Professor in the Department of Urology at Emory University School of Medicine
A phase 1/2 study of detalimogene voraplasmid (EG-70) intravesical monotherapy for patients with high-risk non-muscle invasive bladder cancer (NMIBC)

Abstract #: TPS886
Poster #: J14
Clinical Trial Registration Number: NCT04752722
Session Title: Trials In Progress Poster Session B: Urothelial Carcinoma
Presentation Date/Time: Friday, February 14 from 11:30am-12:45pm PT
Location: Level 1, West Hall
Presenter: Shreyas Joshi, MD, MPH, Assistant Professor in the Department of Urology at Emory University School of Medicine
About Non-Muscle Invasive Bladder Cancer (NMIBC)

Non-muscle invasive bladder cancer (NMIBC) is a disease with a significant patient burden, high clinical needs and massive economic impact on our healthcare system. NMIBC occurs when cancer cells grow in the tissues that line the interior of the bladder, but the cancer has not yet penetrated deeper into the muscle of the bladder wall. About 75-80% of new bladder cancer diagnoses are NMIBC. Patients suffering from high-risk NMIBC who are unresponsive to the standard of care, Bacillus Calmette-Guérin (BCG), face high rates of disease recurrence (50-70%) and are subject to full removal of the bladder (cystectomy) as a curative but life-altering next step.

About Detalimogene Voraplasmid

Detalimogene voraplasmid (formerly known as EG-70) is a novel, investigational, non-viral genetic medicine for patients with high-risk, non-muscle invasive bladder cancer (NMIBC), including Bacillus Calmette-Guérin (BCG)-unresponsive disease. It is designed to be instilled in the bladder and elicit a powerful yet localized anti-tumor immune response.

Detalimogene voraplasmid has received Fast Track designation from the U.S. Food and Drug Administration (FDA) based on its potential to address a high unmet medical need for patients with BCG-unresponsive carcinoma in situ (CIS) NMIBC with or without resected papillary tumors who are unable to undergo cystectomy. Fast Track designation is a process designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need.

Detalimogene was developed using the Company’s Dually Derivatized Oligochitosan (DDX) platform, a technology designed to transform how gene therapies are accessed by patients and utilized by clinicians. Medicines developed with the DDX platform can potentially overcome the limitations of viral-based gene therapies, simplify safe handling and cold storage complexities and streamline both manufacturing processes and administration paradigms.

About the Pivotal LEGEND Trial

Detalimogene voraplasmid is being evaluated in the ongoing, open-label, multi-cohort, Phase 2 LEGEND trial to establish its safety and efficacy in high-risk, non-muscle invasive bladder cancer (NMIBC). LEGEND’s pivotal cohort (Cohort 1) consists of approximately 100 patients with high-risk, Bacillus Calmette-Guérin (BCG)-unresponsive NMIBC with carcinoma in situ (CIS) (with or without papillary disease) and is designed to serve as the basis of the Company’s Biologics License Application (BLA) filing. In addition to this pivotal cohort, three additional cohorts are actively enrolling patients, including NMIBC patients with CIS who are naïve to treatment with BCG (Cohort 2a); NMIBC patients with CIS who have been exposed to BCG, but have not received adequate BCG treatment (Cohort 2b); and BCG-unresponsive high-risk NMIBC patients with papillary-only disease (Cohort 3).

The LEGEND trial is actively enrolling patients with sites participating in the USA, Canada, Europe and the Asia-Pacific region. For more information, please visit TheLegendStudy.com.