On December 2, 2024 TORL BioTherapeutics, LLC (TORL), a clinical stage biotechnology company discovering and developing new antibody-based immunotherapies to improve and extend the lives of patients with cancer worldwide, reported the appointment of Aran Maree, MD, as Chief Medical Officer (Press release, TORL Biotherapeutics, DEC 2, 2024, View Source [SID1234648733]). Additionally, TORL has initiated CATALINA-2, a global Phase 2 study of its novel Claudin 6 (CLDN6) targeted antibody-drug conjugate (ADC) TORL-1-23 in patients with CLDN6 positive (CLDN6+) platinum-resistant ovarian cancer (PROC).

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!

"2024 has been a transformational year for TORL, as the first Phase 2 study with our Claudin 6 targeted antibody-drug conjugate TORL-1-23 is underway and we continue to advance multiple antibody-based clinical programs," said Mark J. Alles, Chairman and Chief Executive Officer of TORL Biotherapeutics. "Aran Maree is among the most accomplished and experienced physician-leaders in the biopharmaceutical industry, and TORL will significantly benefit from his long track record of improving patient outcomes in multiple disease categories and creating corporate value."

Dr. Maree most recently served as Chief Medical Officer for Johnson & Johnson (J&J) Innovative Medicines, the pharmaceuticals segment formerly known as Janssen. In this role, he oversaw a functionally independent team with a primary focus on clinical and scientific advancement of the established products portfolio, patient safety, pediatric portfolio advancement and was co-chair of the company’s R&D Development Committee reviewing the R&D clinical programs across therapeutic modalities in oncology, immunology, neurology, cardiovascular, metabolic and infectious disease. His impact on safety oversight and program development includes some of the most high-profile products in J&J’s history and many other important medicines under development.

Dr. Maree joined J&J in 2006 and held medical roles of increasing responsibility for J&J’s MedTech company in Australia, New Zealand, Asia Pacific and Japan. In these positions, Dr. Maree established a comprehensive medical affairs capability while also leading and strengthening regulatory, quality and health outcomes/access capabilities. In 2012, he was promoted to global Chief Medical Officer of J&J MedTech, responsible for patient monitoring and safety surveillance practices, approaches to clinical data transparency, and scientific integrity at the intersection of biology and technology. In 2017, he was appointed Chief Medical Officer for the pharmaceuticals segment of the company.

Prior to joining J&J, Dr. Maree worked at The Boston Consulting Group and Merck & Co. (MSD) in Australia and New Zealand. Dr. Maree holds an honors medical degree from the Royal College of Surgeons in Ireland/National University of Ireland. He trained as a physician in Dublin, obtaining his Membership of the Royal College of Physicians of Ireland (MRCPI) and in interventional cardiology between Dublin, Ireland and Sydney, Australia.

"The promise of TORL-1-23 and the Company’s growing pipeline of new target programs represent an incredible opportunity to transform clinical practice in oncology," said Aran Maree, MD, Chief Medical Officer. "I am thrilled to be joining the TORL team at such an important time and look forward to establishing and scaling a global medical organization to support the needs of the portfolio and the patients we seek to serve."

"Given our progress discovering and developing antibody-based immunotherapies for a large number of cancer patients, this is the right time for TORL to bring in the Company’s first Chief Medical Officer," said Scientific Co-founder and Board Member Dennis Slamon, MD, PhD, Professor of Medicine, and Chief of the Division of Hematology/Oncology at UCLA’s David Geffen School of Medicine. "Aran’s capability and expertise leading global medical functions and conducting early- to late-stage clinical trials will have an immediate and long-lasting effect on TORL’s ability to bring new compounds to patients as quickly as possible."

In November, TORL initiated CATALINA-2, a global, multi-institutional randomized, open-label Phase 2 study of TORL-1-23 in women with CLDN6+ PROC who have received one to three prior lines of therapy. The study is designed to support accelerated registration in CLDN6+ PROC. CATALINA-2 initiation was supported by Phase 1 data presented at the 2024 European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress, which demonstrated that treatment with TORL-1-23 led to clinically meaningful, durable and confirmed responses with a manageable safety profile in patients with CLDN6+ PROC. Phase 1 evaluation of TORL-1-23 in non-small cell lung cancer and other CLDN6+ cancers is ongoing.

"Since TORL’s founding, we’ve been focused on advancing our portfolio of antibody-based targeted therapies in indications with serious unmet medical need. Initiating our first registrational study and strengthening our leadership team are critical value-creating milestones as we enter our next phase as a Company. Aran’s outstanding multi-decade career and experience will have a significant strategic and operational impact on TORL," said Co-founder, Board Member, President, and Chief Financial Officer Dave Licata.

To date TORL has raised more than $350M from leading global biotechnology investors. In addition to the CLDN6 target, the Company’s pipeline includes programs for Claudin 18.2, Cadherin-17, Delta-like Non-canonical Notch Ligand 1 (DLK1) and other undisclosed targets in both solid tumor and hematologic malignancies.

About Claudin 6

Claudin 6 (CLDN6) is overexpressed in multiple cancers with limited to no detectable expression observed in normal tissues, thus an ideal target for ADC development. CLDN6 is a transmembrane protein important for cell-to-cell connectivity in normal tissues during development but not in adult tissues. Overexpression of CLDN6 occurs in certain malignancies and is implicated in the initiation, progression, and metastasis of certain cancers, including ovarian, non-small cell lung, endometrial, testicular and others. High expression correlates with shortened survival outcomes for patients with ovarian cancer.

About TORL-1-23

TORL-1-23 is a first and potentially best-in-class clinical-stage ADC for the treatment of CLDN6+ solid tumors. The Phase 2 CATALINA-2 study of TORL-1-23 in women with CLDN6+ PROC is currently enrolling. Further details can be found at View Source TORL-1-23 has received Fast Track Designation from the U.S. Food and Drug Administration.

About CATALINA-2

CATALINA-2 is a global, randomized, open-label Phase 2 study of novel CLDN6-targeted ADC TORL-1-23 in women with CLDN6+ PROC who have received one to three prior lines of therapy. The primary endpoint is objective response rate (ORR) per RECIST v1.1 by blinded independent central review. Secondary endpoints include duration of response, ORR by investigator assessment, progression-free survival, overall survival and safety. Further details can be found at View Source

On December 2, 2024 KisoJi Biotechnology Inc., a company focused on the discovery and development of transformative antibody therapeutics, reported that it has raised $41 million in equity, including the conversion of previously funded convertible debentures (Press release, KisoJi Biotechnology, DEC 2, 2024, View Source [SID1234648732]). These funds will be used to advance its lead asset, KJ-103, the first potent naked antibody against TROP2, into the clinic to treat solid tumours. Funds will also be used to deploy its cutting-edge antibody discovery platform towards new multi-specific therapeutic antibody drugs in cardiometabolic disease, as well as immunology and inflammation. The financing was led by Investissement Quebec and Lumira Ventures with participation by Fonds de solidarite FTQ, adMare BioInnovations, and Remiges Ventures.

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!

As previously announced, KisoJi has established a clinical development partnership with Cancer Research UK to bring KisoJi’s lead asset, KJ-103, into a first-in-human clinical trial of approximately 100 patients. KJ-103 is highly differentiated from existing TROP2-targeting drugs on the market or in development, which are antibody drug conjugates (ADCs). KJ-103 does not require a cytotoxic payload but instead functions by recruiting immune cells to kill tumour cells.

The financing will also support the deployment of KisoJi’s cutting-edge antibody discovery platform, including the first of its kind antibody paratope map (KisoSeekTM) that effectively visualizes an immune response against a given target. The Company’s sampling tools allow it to maximize paratope diversity in a directed iterative strategy to focus on distinct antibodies and uncover novel biology, including functional GPCR antibodies.

KisoSeekTM is more efficient and provides greater insights than traditional antibody discovery methods and can integrate seamlessly into existing workflows. All existing data, whether positive or negative, can be used to augment a target specific paratope to supercharge antibody discovery instead of relying on traditional methods of random screening.

KisoJi has also developed a suite of camelid transgenic mice (KisoMouse) that generate single domain antibodies to continue populating the world’s largest single domain antibody database created by KisoJi over the past 8 years. The paratope map and antibody database can be used to generate first-in-class and best-in-class multi-specific antibodies using KisoJi’s modular multi-specific antibody format (KisoBodyTM). The KisoBodyTM is easily customizable and manufacturable with tri-specific antibody titers at greater than 6 g/L in commercial production cell lines.

Bicha Ngo, President and CEO, Investissement Québec, said: "By contributing to KisoJi Biotechnology’s financing round, Investissement Québec is reaffirming its commitment to supporting innovative companies in the life sciences industry, a key sector for the Québec economy. This funding will allow KisoJi Biotechnology to hit critical milestones in its operations, from completing preclinical activities to launching clinical trials, notably through a landmark agreement with Cancer Research UK, one of the world’s largest funders of cancer research, all the while helping move innovations from the R&D stage to the marketplace."

Daniel Hétu, Managing Director, Lumira Ventures, said: "KisoJi has built a truly differentiated, AI enabled and comprehensive antibody discovery platform leveraging the deep expertise of their team that spans transgenic mice, single-domain antibodies and AI. Lumira is proud to have supported the development of KisoJi’s innovative platform from its inception and we look forward to continuing to work with the company and our co-investors as KisoJi transitions its propriety programs to the clinical stage.

Maxime Pesant, Vice-President Private Equity and Impact Investing | Life Sciences, Fonds de solidarité FTQ, said: "The Fonds de solidarité FTQ is proud to reiterate its commitment to KisoJi, an innovative company of which we have been partners from the very beginning alongside Lumira. Our strategic investments in the sector help propel high-potential biotechs to new heights. With major expertise in the life sciences field and with our long-term presence, the Fund continues to support high-impact companies like KisoJi, paving the way for groundbreaking innovations and significant medical advancements."

David Young, co-founder and CEO of KisoJi said: "Through the support of our new and existing investors, this financing will enable KisoJi to continue its development of pipeline assets in oncology, cardiometabolic and immunology indications using our cutting-edge platform and AI tools."

Evolution Venture Partners acted as the exclusive strategic advisor to KisoJi in connection with the financing.

On December 2, 2024 Autolus Therapeutics plc (Nasdaq: AUTL), an early-commercial stage biopharmaceutical company developing next-generation programmed T cell therapies, reported that the New England Journal of Medicine has published data from the pivotal Phase 1b/2 FELIX study of obecabtagene autoleucel (obe-cel) in relapsed/refractory (r/r) adult B-cell Acute Lymphoblastic Leukemia (ALL) (Press release, Autolus, DEC 2, 2024, View Source [SID1234648731]). The data demonstrate high rates of durable responses with low incidence of grade ≥3 immune-related toxicity.

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!

"With its low rates of serious side effects coupled with compelling long-term survival data and durable responses, obe-cel offers real hope for adult lymphoblastic leukemia patients," said Dr. Claire Roddie, MD, PhD, FRCPath, Lead investigator of the FELIX study and Associate Professor of Haematology at the University College London (UCL) Cancer Institute. "Obe-cel’s durable responses were particularly observed in patients with low-intermediate bone marrow burden, including patients who did not receive consolidative allo-Stem Cell Transplant and there could be an opportunity to use obe-cel as earlier-line consolidation."

"Adult ALL is an extremely aggressive cancer and patients with this disease historically suffer from poor outcome," said Elias Jabbour, MD, U.S. lead investigator of the FELIX study and professor of Leukemia, ALL Section Chief, at The University of Texas MD Anderson Cancer Center, Houston, Texas. "The clinical benefit and improvements in survival demonstrated by obe-cel have the potential to redefine the standard of care in the adult relapsed/refractory B-ALL setting."

Of the 153 r/r B-ALL patients enrolled patients in the FELIX study, 127 (83.0%) received at least one obe-cel infusion and were evaluable. Eligible patients underwent leukapheresis, and bridging therapy, except blinatumomab, was permitted at the investigator’s discretion. Obe-cel was administered in a bone marrow (BM) burden adjusted split dose following lymphodepletion, with a BM mandated prior to lymphodepletion to guide dosing. The second obe-cel dose was given in the absence of severe/unresolved toxicity.

The primary end point was overall remission (CR/CRi). In the pivotal cohort of patients, (cohort IIA (n=94)), the CR/CRi for patients who received at least one infusion of obe-cel was 76.6% Across all infused patients (n=127), of the 91/127 with ≥5% BM blasts pre-lymphodepletion, the CR/CRi was 74.7%. Median response duration for all infused patients was 21.2 months. Median event-free survival (EFS) was 11.9 months and the estimated 6- and 12-month event-free survival rates were 65.4% and 49.5%, respectively. BM burden pre-lymphodepletion correlated with median event-free survival; patients with low (<5% BM blasts), intermediate (≥5–≤75% blasts), and high (>75% blasts) BM burden had event-free survival rates at 12 months of 68.0%, 54.9% and 25.0%, respectively.

Median overall survival (OS) was 15.6 months and estimated 6- and 12-month overall survival rates were 80.3% and 61.1%, respectively. BM burden pre-lymphodepletion correlated with overall survival; patients with low, intermediate, and high BM burden had an overall survival rate at 12 months of 71.5%, 58.7% and 55.0%, respectively. BM burden before enrollment also influenced event-free and overall survival.

Of the 127 patients infused (pooled across all study cohorts), 99 patients responded. Of the responders, 18 patients (18.2%) proceeded to allo-Stem Cell Transplant (allo-SCT) while in remission at a median of 101 days post-obe-cel infusion. In 6/18 (33.3%), this was a second allo-SCT. Of 11 patients who had persisting CAR T cells before allo-SCT, and who had samples available post, none had CAR T cells detected following allo-SCT. There was no difference in event-free and overall survival observed between patients who received allo-SCT and those who did not.

Median duration of CAR T persistence by droplet digital PCR (ddPCR) in peripheral blood was 17.8 months.

Obe-cel was associated with minimal immunotoxicity. CRS and Immune effector cell-associated neurotoxicity syndrome (ICANS) rates (Grade ≥3) were 2.4% and 7.1%, respectively. Overall, 87 (68.5%) patients developed CRS, and 29 (22.8) developed ICANS. Severe ICANS post-obe-cel were seen as largely limited to patients with high BM burden pre-lymphodepletion. Intensive care unit (ICU) admissions occurred in 20 (15.7%) patients for a median of 5.5 days (range,1−37) of which 7/20 were admitted due to immunotoxicity management (5 ICANS, 2 CRS).

Obe-cel was approved by the Food & Drug Administration (FDA) under the brand name AUCATZYL (obecabtagene autoleucel) on November 8, 2024. Marketing authorization applications (MAAs) for obe-cel [in adult r/r ALL] are being reviewed by the regulators in both the EU and the UK, with a submission to the European Medicines Agency (EMA) accepted in March 2024, and a submission accepted by the UK MHRA in August 2024.

On December 2, 2024 MacroGenics, Inc. (Nasdaq: MGNX), a biopharmaceutical company focused on discovering, developing, manufacturing and commercializing innovative monoclonal antibody-based therapeutics for the treatment of cancer, reported that the Company’s management will participate in the following investor conference this month (Press release, MacroGenics, DEC 2, 2024, View Source [SID1234648730]):

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!

7th Annual Evercore HealthCONx (Coral Gables, FL). MacroGenics’ President and Chief Executive Officer, Scott Koenig, M.D., Ph.D., will participate in a fireside chat on Wednesday, December 4, 2024, at 7:30am ET. MacroGenics’ management will also participate in one-on-one meetings.

A webcast of the above presentation may be accessed under "Events & Presentations" in the Investor Relations section of MacroGenics’ website at View Source The Company will maintain an archived replay of this webcast on its website for 30 days.

On December 2, 2024 UroGen Pharma Ltd. (Nasdaq: URGN), a biotech company dedicated to developing and commercializing innovative solutions that treat urothelial and specialty cancers, reported that new data on UGN-102 (mitomycin) for intravesical solution, JELMYTO (mitomycin) for pyelocalyceal solution, and UGN-301(zalifrelimab intravesical solution) will be presented at the Society of Urologic Oncology (SUO) 2024 annual meeting being held in Dallas, Texas from December 4 – 6 (Press release, UroGen Pharma, DEC 2, 2024, View Source [SID1234648729]).

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 the SUO has accepted data highlighting the potential of our investigational treatment, UGN-102, in development for patients with low-grade, intermediate-risk non-muscle-invasive bladder cancer (LG-IR-NMIBC), as well as the ongoing clinical value of JELMYTO for treating low-grade upper tract urothelial carcinoma (LG-UTUC)," said Mark Schoenberg, M.D., Chief Medical Officer of UroGen. "These presentations underscore our ongoing commitment to addressing the critical unmet needs of patients with urothelial cancers, as well as our mission to provide innovative treatment options that seek to improve both outcomes and quality of life for those battling these challenging conditions."

Key details of UGN-102, JELMYTO and UGN-301 abstracts accepted by SUO:

Abstract Title

Schedule

Presenter

PRIMARY CHEMOABLATION OF RECURRENT LOW-GRADE INTERMEDIATE-RISK NON-MUSCLE-INVASIVE BLADDER CANCER WITH UGN-102: A SINGLE-ARM, OPEN-LABEL, PHASE 3 TRIAL (ENVISION)

Poster 121

Date: 12/5

Time: 2:15-3:15 pm CT

Dr. Max Kates

LONG-TERM OUTCOMES OF PRIMARY CHEMOABLATION OF LOW-GRADE UPPER TRACT UROTHELIAL CARCINOMA (LG-UTUC) WITH UGN-101, A MITOMYCIN REVERSE THERMAL GEL

Poster 122

Date: 12/5

Time: 2:15-3:15 pm CT

Dr. Brian Hu

HOME INSTILLATION OF UGN-102 FOR PRIMARY CHEMOABLATION OF RECURRENT LOW-GRADE INTERMEDIATE-RISK NON-MUSCLE-INVASIVE BLADDER CANCER: A SINGLE-ARM, OPEN-LABEL, PHASE 3B TRIAL

Poster 124

Date: 12/5

Time: 2:15 – 3:15 pm CT

Dr. Vincent Michael Bivins

A PHASE 1 DOSE-ESCALATION STUDY OF UGN-301 (ZALIFRELIMAB) IN PATIENTS WITH RECURRENT NON-MUSCLE INVASIVE BLADDER CANCER (NMIBC)

Poster 133

Date: 12/5

Time: 2:15 – 3:15 pm CT

Caretha L. Creasy

A PHASE 1 DOSE-ESCALATION STUDY OF UGN-301 (ZALIFRELIMAB) AS MONOTHERAPY AND IN COMBINATION WITH OTHER AGENTS IN PATIENTS WITH RECURRENT NON-MUSCLE INVASIVE BLADDER CANCER (NMIBC)

Poster 206

Date: 12/6

Time: 10:00 – 11:00 am CT

Caretha L. Creasy

For further information about UroGen’s ongoing clinical trials and programs, please visit our website at urogen.com to learn more or follow us on X (Twitter), @UroGenPharma.

About UGN-102

UGN-102 (mitomycin) for intravesical solution is an innovative drug formulation of mitomycin, currently in Phase 3 development for the treatment of LG-IR-NMIBC. Utilizing UroGen’s proprietary RTGel technology, a sustained release, hydrogel-based formulation, UGN-102 is designed to enable longer exposure of bladder tissue to mitomycin, thereby enabling the treatment of tumors by non-surgical means. UGN-102 is delivered to patients using a standard urinary catheter in an outpatient setting by a trained healthcare professional. UroGen completed the NDA submission in August, ahead of schedule. The FDA accepted the NDA for UGN-102 and assigned a PDUFA goal date of June 13, 2025.

About JELMYTO

JELMYTO (mitomycin) for pyelocalyceal solution is a mitomycin-containing reverse thermal gel containing 4 mg mitomycin per mL gel indicated for the treatment of adult patients with LG-UTUC. It is recommended for primary treatment of biopsy-proven LG-UTUC in patients deemed appropriate candidates for renal-sparing therapy. JELMYTO is a viscous liquid when cooled and becomes a semi-solid gel at body temperature. The drug slowly dissolves over four to six hours after instillation and is removed from the urinary tract by normal urine flow and voiding. It is approved for administration in a retrograde manner via ureteral catheter or antegrade through nephrostomy tube. The delivery system allows the initial liquid to coat and conform to the upper urinary tract anatomy. The eventual semisolid gel allows for chemoablative therapy to remain in the collecting system for four to six hours without immediately being diluted or washed away by urine flow.

UGN-301

UGN-301 is our investigational, in-licensed, anti-CTLA-4 monoclonal antibody (zalifrelimab), prepared with reverse-thermal hydrogel for intravesical administration into the bladder. Intravesical administration of UGN-301 is designed to increase drug concentrations in the bladder without significant systemic exposure, potentially diminishing the systemic toxicity associated with CTLA-4 blockade. UroGen is evaluating UGN-301 as combination therapy for the intravesical treatment of high-grade NMIBC.