On September 24, 2024 Astellas Pharma Inc. (TSE:4503, President and CEO: Naoki Okamura, "Astellas") reported that Japan’s Ministry of Health, Labour and Welfare (MHLW) has approved PADCEV (enfortumab vedotin [genetical recombination]) with MSD’s KEYTRUDA (pembrolizumab [genetical recombination]) as a combination therapy for the first-line treatment of adult patients with radically unresectable urothelial carcinoma (Press release, Astellas, SEP 24, 2024, View Source,-Labour-and-Welfare-Approves-PADCEV-TM-enfortumab-vedotin-with-KEYTRUDA-R-pembrolizumab-for-First-Line-Treatment-of-Radically-Unresectable-Urothelial-Carcinoma [SID1234646833]). This is the first approved combination treatment for radically unresectable urothelial cancer in Japan to offer an alternative to platinum-containing chemotherapy, the current standard of care for first-line treatment.

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!

In Japan, bladder cancer is the 9th most common cancer, with over 34,500 new cases diagnosed and 11,000 deaths reported from the disease in 2022.3 Particularly poor outcomes are associated with the latter stages of the disease, with global five-year survival rates of 39% and 8% for locally advanced and metastatic urothelial cancer, respectively.4

The approval by the MHLW was supported by results from the Phase 3 EV-302 clinical trial (also known as KEYNOTE-A39) which explored the efficacy and safety of enfortumab vedotin in combination with pembrolizumab in patients with previously untreated locally advanced or metastatic urothelial cancer (la/mUC). Results showed that the treatment combination resulted in a median overall survival of 31.5 months (95% CI: 25.4-NR) compared to 16.1 months (95% CI: 13.9-18.3) with platinum-containing chemotherapy, representing a 53% reduction in risk of death (Hazard Ratio [HR]=0.47; 95% Confidence Interval [CI]: 0.38-0.58; P<0.00001). The median progression-free survival of 12.5 months (95% CI: 10.4-16.6) with the combination compared to 6.3 months (95% CI: 6.2-6.5) with chemotherapy represents a 55% reduction in the risk of cancer progression or death (HR=0.45; 95% CI: (0.38-0.54); P<0.00001). The safety results in EV-302 are consistent with those previously reported for this combination in EV-103 in cisplatin-ineligible patients with la/mUC. The most common (≥3%) Grade 3 or higher adverse events (AEs) related to treatment with enfortumab vedotin in combination with pembrolizumab were maculo-papular rash, hyperglycemia, neutropenia, peripheral sensory neuropathy, diarrhea, and anemia. No new safety issues were identified. During the EV-302 trial, approximately 30% of patients completed treatment with chemotherapy and then went on to receive maintenance therapy with avelumab, a PD-L1 inhibitor, which is reflective of current real world clinical practice.1 Results were presented at the 2023 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress and published in the New England Journal of Medicine.1

Ahsan Arozullah, M.D., M.P.H., Senior Vice President, Head of Oncology Development, Astellas
"Today’s approval by Japan’s MHLW expands the benefits of treatment with enfortumab vedotin in combination with pembrolizumab to patients living with radically unresectable urothelial carcinoma in Japan. These patients will now have an alternative to platinum-containing chemotherapy to treat this devastating disease, helping to improve patient outcomes, extend lives and give further hope to the patients and families that we serve."

In addition to this latest approval, enfortumab vedotin in combination with pembrolizumab was approved by the European Commission in August 2024 for the first-line treatment of adult patients with unresectable or metastatic urothelial cancer, who are eligible for platinum-containing chemotherapy. Furthermore, in December 2023, the U.S. Food and Drug Administration approved the use of the combination therapy for adult patients with locally advanced or metastatic urothelial cancer.

Astellas has already reflected the impact from the approval for enfortumab vedotin in Japan in its financial forecast for the current fiscal year ending March 31, 2025.

About EV-302
The EV-302 trial is an open-label, randomized, controlled Phase 3 study, evaluating enfortumab vedotin in combination with pembrolizumab versus platinum-containing chemotherapy in patients with previously untreated la/mUC. The study enrolled 886 patients with previously untreated la/mUC who were eligible for cisplatin- or carboplatin-containing chemotherapy regardless of PD-L1 status. Patients were randomized to receive either enfortumab vedotin in combination with pembrolizumab or platinum-containing chemotherapy. The dual primary endpoints of this trial are OS and PFS per RECIST v1.1 by blinded independent central review (BICR). Select secondary endpoints include ORR per RECIST v1.1 by BICR, DOR per RECIST v1.1 by BICR, and safety.1

The EV-302 trial is part of an extensive clinical program evaluating this combination in multiple stages of urothelial cancer and other solid tumors. Findings from EV-302 were presented at the 2023 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress and published in the New England Journal of Medicine.1

About Bladder and Urothelial Cancer
Urothelial cancer, or bladder cancer, begins in the urothelial cells, which line the urethra, bladder, ureters, renal pelvis, and some other organs.5 Urothelial cancer accounts for 90% of global bladder cancers and can also be found in the renal pelvis, ureter, and urethra.6,7 If bladder cancer has spread to surrounding organs or muscles, it is called locally advanced disease.8 If the cancer has spread to other parts of the body, it is called metastatic disease.9 Globally, approximately 12% of cases are locally advanced or metastatic urothelial cancer at diagnosis.10

About PADCEV (enfortumab vedotin [genetical recombination])
PADCEV (enfortumab vedotin [genetical recombination]) is a first-in-class antibody-drug conjugate (ADC) that is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer.11,12 Non-clinical data suggest the anticancer activity of enfortumab vedotin is due to its binding to Nectin-4-expressing cells, followed by the internalization and release of the anti-tumor agent monomethyl auristatin E (MMAE) into the cell, which result in the cell not reproducing (cell cycle arrest) and in programmed cell death (apoptosis).11

PADCEV is indicated in Japan as monotherapy for the treatment of adult patients with radically unresectable urothelial carcinoma that has progressed after anti-cancer chemotherapy, and in combination with KEYTRUDA (pembrolizumab) for the first-line treatment of adult patients with radically unresectable urothelial carcinoma.13

Ongoing Investigational Trials
EV-302 (NCT04223856) is an open-label, randomized, controlled Phase 3 trial, evaluating enfortumab vedotin in combination with pembrolizumab versus platinum-containing chemotherapy in patients with previously untreated locally advanced or metastatic urothelial cancer (la/mUC) who were eligible for cisplatin- or carboplatin-containing chemotherapy regardless of PD-L1 status.

EV-103 (NCT03288545) is an ongoing, multi-cohort, open-label, multicenter Phase 1b/2 trial investigating enfortumab vedotin alone or in combination with pembrolizumab and/or chemotherapy in first- or second-line settings in patients with la/mUC and in patients with muscle-invasive bladder cancer (MIBC).

Enfortumab vedotin in combination with pembrolizumab is being investigated in an extensive program in multiple stages of urothelial cancer, including two Phase 3 clinical trials in MIBC in EV-304 (NCT04700124, also known as KEYNOTE-B15) and EV-303 (NCT03924895, also known as KEYNOTE-905). The use of enfortumab vedotin in combination with pembrolizumab in second-line urothelial cancer and MIBC has not been proven safe or effective.

EV-203 (NCT04995419) is a Phase 2, multicenter, single-arm bridging trial in China designed to evaluate the efficacy, safety, and pharmacokinetic performance of enfortumab vedotin as treatment for patients in China. A total of 40 patients were enrolled in the trial.

EV-104 (NCT05014139) is a Phase 1 trial exploring enfortumab vedotin in patients with non-muscle invasive bladder cancer (NMIBC). The trial will be conducted in two-parts, assessing dose escalation and dose expansion with enfortumab vedotin when administered intravesically as a monotherapy.

EV-202 (NCT04225117) is an ongoing, multi-cohort, open-label, multicenter Phase 2 trial investigating enfortumab vedotin alone in patients with previously treated advanced solid tumors. This trial also has a cohort that is investigating enfortumab vedotin in combination with pembrolizumab in patients with previously untreated recurrent / metastatic head and neck squamous cell carcinoma.

Important Safety Information
For important Safety Information for PADCEV, please see the Package Insert.

On September 24, 2024 Anixa Biosciences, Inc. ("Anixa" or the "Company") (NASDAQ: ANIX), a biotechnology company focused on the treatment and prevention of cancer, reported its strategic plan for a Phase 2 study for its breast cancer vaccine (Press release, Anixa Biosciences, SEP 24, 2024, View Source [SID1234646849]). The Phase 1 trial is being conducted at Cleveland Clinic, funded by a grant from the U.S. Department of Defense.

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 proposed Phase 2 trial will evaluate the efficacy of the vaccine administered in the neoadjuvant (before surgery) setting, in combination with chemotherapy and Keytruda (pembrolizumab). The goal of neoadjuvant therapy is to reduce tumor burden and to prevent tumor recurrence with the intent to improve survival. This clinical trial approach allows Anixa to enroll a broader range of patients, encompassing multiple types of breast cancer. The therapeutic market for breast cancer is large due to the increase in prevalence of breast cancer and an increase in screening resulting in a demand for treatment. Compared with primary prevention, the development path for breast cancer treatment is expected to have a shorter path to approval. The therapeutic market covers all stages of breast cancer, from early to advanced and metastatic cases. In 2023, the market was valued at approximately $38.35 billion and is projected to reach $89.67 billion by 2030, growing at a compound annual growth rate (CAGR) of 12.9% (Maximize Market Research).

The key objectives of the trial include evaluating the immunological response to the vaccine and comparing clinical efficacy of standard of care therapy alone with the vaccine plus standard of care therapy. A key component of this trial will be the evaluation of breast cancer tissue and the validation of the immunological mechanism of action of the vaccine.

The trial is expected to commence in 2025 and is projected to last approximately two to three years. Immunological responses to the vaccine will be made available as the trial advances, providing a faster and more cost-effective path toward potential approval and/or partnerships with pharmaceutical companies.

"We are excited to unveil our Phase 2 study plan, bringing us one step closer to a potentially transformative therapy for breast cancer patients," said Dr. Amit Kumar, Chairman and CEO of Anixa Biosciences. "By targeting treatment rather than prevention, we can reach a broader patient population and potentially expedite the process of regulatory approval and partnerships. This trial marks a key milestone in advancing our mission to fight cancer through innovative therapies. While our Phase 2 trial focuses on the therapeutic market, with the data obtained in this trial, we expect to conduct additional, more informed studies for both recurrence prevention and primary prevention with partners in the future."

Initial Phase 1 data was presented at the San Antonio Breast Cancer Symposium in December 2023. The data showed no safety concerns, with protocol defined immune responses observed in a majority of patients. Additional data from the Phase 1 trial will be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting in early November 2024.

The Phase 1 trial is conducted in collaboration with Cleveland Clinic and is funded by a grant from the U.S. Department of Defense. Anixa is the exclusive worldwide licensee of the novel breast cancer vaccine technology developed at Cleveland Clinic. The grant funding from the U.S. Department of Defense was provided to Cleveland Clinic.

On September 24, 2024 Circio Holding ASA (OSE: CRNA), a biotechnology company developing next generation circular RNA vector technology for gene therapy, reported that a scientific abstract submitted to the European Society of Cell and Gene Therapy (ESGCT) annual meeting 2024 has been selected for oral presentation (Press release, Circio, SEP 24, 2024, View Source [SID1234646834]). The presentation will be given by Circio´s CTO, Dr. Thomas B Hansen on 23 October 2024.

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!

"Circio´s unique and powerful circVec platform keeps building momentum, and we are very excited to be selected to present our technology at the prestigious ESGCT meeting." said Dr. Thomas B. Hansen, CTO of Circio "This meeting provides a great opportunity to showcase how the latest circVec generation continues to significantly outperform mRNA-based expression, thereby delivering a substantial improvement over current gold-standard gene therapy approaches."

The ESGCT invitation follows recent presentations at several RNA industry conferences and coverage in international life science media, highlighting the advantages and potential of circular RNA therapeutics and reinforcing Circio´s position as a leader in this rapidly emerging field.

Title of presentation:

Optimization of in vitro and in vivo performance of circVec, a vector-based circular RNA expression platform for enhanced gene therapy

Presenter:

Dr. Thomas B Hansen, CTO

Time and location:

23 October 2024 @ 19:30hrs CET – Rome, Italy

On September 24, 2024 Amarex reported its work on behalf of Gibson Oncology has resulted in an Orphan Drug Designation (ODD) by the United States Food and Drug Administration (FDA) for the drug LMP744 (Press release, Amarex Clinical Research, SEP 24, 2024, View Source [SID1234646850]).

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!

LMP744 treats gliomas, readily crossing the blood brain barrier (BBB) at 10 times the concentration required to kill cancer cells and sustains a high concentration for over 24 hours per dose.

"For decades glioblastoma brain cancer patients have not seen appreciable increases in overall survival rates with Temodar, the current standard of care treatment," said Mr. Randall Riggs, President & CEO of Gibson Oncology. "Our goal is to advance both LMP400 and LMP744 to market via the shortest and quickest path, thus benefiting cancer patients in need."

Obtaining ODD for LMP744 for all gliomas underscores the promising and novel treatment of the drug to inhibit two cancer targets: TOPO 1 and downregulate cMyc overexpression through the drug’s potent binding of the G4 quadruplex of cMyc.

"This crucial designation could not come at a more critical time for the families who are fighting this disease," said Dr. Kush Dhody, President, Amarex. "Reaching this milestone sets the company up for future success and, most importantly, poises Gibson Oncology to continue its path to commercialization of this life-saving treatment."

Through a multi-year collaboration with cMyc expert, Dr. Danzhou Yang of Purdue University, Gibson Oncology discovered that LMP400, which received ODD earlier in the year, and LMP744 are potent nM inhibitors of both TOPO 1 and cMyc oncogene. Together, the teams determined that LMP744, a small molecule, selectively targets two well-known drivers of human cancers, cMyc oncogene and TOPO 1.

The discovery of this compound’s unique anti-cancer mechanism of action (MOA) allowed Gibson Oncology to better position LMP744 and LMP400 to cancer targets with high unmet medical needs.

Presently, LMP744 and LMP400 is positioned to enter a Phase 2 human clinical trial in recurrent gliomas in collaboration with the National Institutes of Health (NIH).

Gibson Oncology believes it is important to leverage the Orphan Drug Designation both drugs have received from the FDA for all gliomas, not just glioblastomas, which includes children with gliomas. Rapid regulatory advancement empowers LMP400 and LMP744 to the shortest and quickest path to market, thus benefiting cancer patients in need.

On September 24, 2024 Duke Street Bio Ltd, a precision medicine biotech developing next generation small molecule cancer therapies, reported that the European Medicines Agency (EMA) has granted approval to commence a clinical trial for its highly-selective PARP1 inhibitor, DSB2455 (Press release, Duke Street Bio, SEP 24, 2024, View Source [SID1234646835]). This potentially best-in-class, potent, highly selective and CNS-penetrant agent targets cancers that harbour homologous recombination deficiencies (HRD) including BRCA mutations. The safety profile of first generation non-selective PARP1/2 inhibitors has restricted their application, particularly in combination with chemotherapy and radiotherapy. By selectively inhibiting PARP1, we believe that DSB2455 has the potential to achieve a significantly enhanced therapeutic index, representing a significant advancement in precision medicine cancer treatment. Preliminary data indicate a strong safety profile and compelling efficacy in preclinical studies, paving the way to open our trial in the clinic.

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!

Alan Wise, CEO of Duke Street Bio, commented, "The approval of the DSB2455 First-in-Human clinical trial by the EMA is a testament to the therapeutic potential of our innovative approach in the DDR space. Duke Street Bio’s mission is to improve patient outcomes and bring new hope to individuals battling cancer. We believe that DSB2455 has the potential for improved efficacy and tolerability versus first-generation PARP inhibitors in patient populations where there is still significant unmet medical need."