On December 5, 2024 NextCure presented its corporate presentation (Presentation, NextCure, DEC 5, 2024, View Source [SID1234648826]).

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On December 5, 2024 UroGen Pharma Ltd. (Nasdaq: URGN), a biotech company dedicated to developing and commercializing innovative solutions that treat urothelial and specialty cancers, reported the presentation of the Phase 3 ENVISION trial’s efficacy and safety results at the Society of Urologic Oncology (SUO) annual meeting in Dallas, TX (Press release, UroGen Pharma, DEC 5, 2024, View Source [SID1234648834]). These results, published online in the Journal of Urology in October, demonstrate that treatment with investigational therapy UGN-102, a mitomycin-based intravesical solution, resulted in a high and clinically meaningful complete response rate that was durable in patients with recurrent low-grade intermediate-risk non-muscle-invasive bladder cancer (LG-IR-NMIBC).

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"Finding options for patients with recurrent low-grade bladder cancer continues to be a major unmet need," says Max Kates, R. Christian B. Evensen Professor and an Associate Professor of Urology and Oncology, and Director, Division of Urologic Oncology at the Brady Urological Institute at Johns Hopkins and ENVISION study investigator. "We are excited by the overall results of the ENVISION trial, especially the durability of response data, that support the potential of UGN-102 as a viable treatment option for these patients."

In the ENVISION study, UGN-102 treatment showed an impressive 82.3% (95% CI: 75.9%, 87.1%) duration of response (DOR) at 12 months, according to the Kaplan-Meier estimate, in patients who achieved a complete response (CR) at 3 months following the initial treatment with UGN-102. The DOR at 15 months (n=43) and 18 months (n=9) remained robust, both at 80.9% (95% CI: 73.9%, 86.2%) according to the Kaplan-Meier estimates. These results build upon the trial’s positive primary endpoint, a 79.6% (95% CI: 73.9%, 84.5%) CR rate 3 months after the first instillation of UGN-102.

The side effect profile of UGN-102 was consistent with previous clinical trials, further supporting its potential as a new treatment option for patients with LG-IR-NMIBC.

"We are excited by the progress made in advancing UGN-102 as a potential treatment for LG-IR-NMIBC and securing a PDUFA goal date of June 13, 2025, from the FDA," said Mark Schoenberg, M.D., Chief Medical Officer, UroGen. "The strong durability of response observed in the ENVISION study highlights UGN-102’s promising potential for patients. Given that many LG-IR-NMIBC patients are elderly and endure multiple surgeries under general anesthesia for their condition that impact their health and quality of life, there is an urgent need for alternative treatment options that can prolong recurrence-free periods and enhance patient outcomes."

The most common treatment-emergent adverse events (TEAEs) in the ENVISION trial were dysuria, hematuria, urinary tract infection, pollakiuria, fatigue, and urinary retention. TEAEs were typically mild-to-moderate in severity and resolved or resolving. The ENVISION trial demonstrated a similar safety profile to that observed in other studies of UGN-102.

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 treat tumors by enabling longer exposure of bladder tissue to mitomycin. 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 for UGN-102 in August, ahead of schedule. The FDA accepted the NDA for UGN-102 and assigned a PDUFA goal date of June 13, 2025.

About Non-Muscle Invasive Bladder Cancer (NMIBC)

In the U.S., bladder cancer is the second most common urologic cancer in men. LG-IR-NMIBC represents approximately 22,000 newly diagnosed bladder cancer patients each year and an estimated 60,000 recurrences annually among patients diagnosed from previous years. Bladder cancer primarily affects older populations with increased risk of comorbidities, with the median age of diagnosis being 73 years. Guideline recommendations for the management of NMIBC include trans-urethral resection of bladder tumor (TURBT) as the standard of care. Up to 70 percent of NMIBC patients experience at least one recurrence and LG-IR-NMIBC patients are even more likely to recur and face repeated TURBT procedures. LG-IR-NMIBC is characterized by early or frequent recurrences, multiple tumors, or a solitary tumor larger than three centimeters.

About ENVISION

The Phase 3 ENVISION trial is a single-arm, multinational, multicenter study evaluating the efficacy and safety of UGN-102 (mitomycin) for intravesical solution as a therapy for patients with LG-IR-NMIBC. The Phase 3 ENVISION trial completed target enrollment with approximately 240 patients across 56 sites. Study participants received six once-weekly intravesical instillations of UGN-102. The primary endpoint evaluated the CR rate at the three-month assessment after the first instillation, and the key secondary endpoint evaluated durability over time in patients who achieved a CR at the three-month assessment. Learn more about the Phase 3 ENVISION trial at www.clinicaltrials.gov (NCT05243550).

On December 5, 2024 Simcha Therapeutics ("Simcha"), a clinical-stage immunobiology company pioneering first-in-class cytokine treatments in cancer, reported the opening of two clinical studies assessing the use of ST-067, Simcha’s decoy-resistant IL-18, in hematological indications (Press release, Simcha Therapeutics, DEC 5, 2024, View Source [SID1234648850]). One study (ClinicalTrials.gov ID NCT06492707) will assess ST-067 in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), while the other study (ClinicalTrials.gov ID NCT06588660) will test ST-067 in combination with teclistamab (TECVAYLI) in patients with multiple myeloma.

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"These two studies, both of which may rapidly generate clinical proof-of-concept data in indications where there is significant need for better therapies, represent a very exciting opportunity for us to explore additional therapeutic areas that have great potential to respond well to treatment with IL-18," said Sanuj Ravindran, M.D., chief executive officer of Simcha. "Emerging data, including those included in our preclinical poster to be presented at ASH (Free ASH Whitepaper), are generating signals that serve as proof-of-concept and point to the therapeutic potential of IL-18 across various hematological cancers, so we are pleased to partner with leading hematologic cancer experts on these trials."

The AML/MDS study, under principal investigator Elizabeth Krakow, M.D., of Fred Hutch Cancer Center, is enrolling patients over 18 years of age who have persistent or recurrent AML or MDS after hematopoietic cell transplantation (HCT), also known as a bone marrow transplant. While HCT is the only curative therapy for most forms of AML or MDS, relapse occurs in approximately one-third of patients and is the most common cause of death following HCT.

The Phase 1, open-label, dose-escalation study will primarily assess dose limiting toxicities and the number of clinical trial subjects who complete four consecutive weeks of treatment with ST-067. Secondary endpoints will assess response rates, overall survival and whether graft-versus-leukemia effects can be elicited without the accompanying graft-versus-host disease.

The study assessing ST-067 in combination with teclistamab, a bi-specific antibody with T cell engagement activity, in patients 18 years of age or older with relapsed or refractory multiple myeloma is occurring under the direction of Rahul Banerjee, M.D., of the University of Washington and Fred Hutch Cancer Center. This open-label Phase 1b study will primarily assess dose-limiting toxicities of ST-067 alone and in combination with teclistamab, as well as optimal dosing and the incidence of adverse events. Secondary endpoints will include overall response rate, duration of response, progression-free survival, overall survival and measurable residual disease negativity.

T-cell directed therapeutics, like teclistamab, other bi-specific antibodies or CAR Ts, have become standards of care for the treatment of relapsed/refractory multiple myeloma. However, they are not curative, as not all patients respond to teclistamab, and relapse can occur in those that do. The multiple myeloma study is based on the hypothesis that ST-067 in combination with teclistamab will promote T-cell fitness and persistence, which could increase the number of patients who respond to teclistamab and lengthen durations of response.

Data to be highlighted at ASH (Free ASH Whitepaper) in a poster presentation demonstrate the therapeutic activity of decoy-resistant IL-18 in multiple mouse models of hematological tumors including B-cell lymphoma, acute myeloid leukemia and plasma cell myeloma. The poster, entitled "Preclinical Efficacy of Decoy-Resistant IL-18 in Hematological Malignancies" will be presented during poster session 802 on Monday, December 9 from 6:00 PM to 8:00 PM.

In addition, a trials in progress poster describing the AML/MDS study will be presented at ASH (Free ASH Whitepaper). The poster, entitled "Trials in Progress: Decoy-Resistant Interleukin-18 (DR-18) for Relapse or Pre-Emptive Treatment of Measurable Residual Disease after Allogeneic Hematopoietic Cell Transplantation in Patients with AML and MDS: DR. DREAM, a Phase I Trial (NCT06492707)" will be presented Monday, December 9 from 6:00 PM to 8:00 PM in poster session 701.

On December 5, 2024 Protara Therapeutics, Inc. (Nasdaq: TARA), a clinical-stage company developing transformative therapies for the treatment of cancer and rare diseases, reported results from its ongoing Phase 2 open-label ADVANCED-2 trial (Press release, Protara Therapeutics, DEC 5, 2024, View Source [SID1234648827]). The trial is assessing intravesical TARA-002, the Company’s investigational cell-based therapy, in high-risk Non-Muscle Invasive Bladder Cancer (NMIBC) patients with carcinoma in situ or CIS (± Ta/T1) who are Bacillus Calmette-Guérin (BCG)-Unresponsive or BCG-Naïve. The complete response (CR) rate across BCG exposures was 72% (13/18) at six months and 70% (14/20) at any time with 100% (9/9) of patients maintaining a CR from three months to six months. In addition, two of three patients maintained a CR at nine months. These results will be featured today during a poster session at the 25th Annual Meeting of the Society of Urologic Oncology (SUO) in Dallas, Texas.

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The dataset includes 20 patients who were evaluable at three months, 18 patients who were evaluable at six months and three patients who were evaluable at nine months with a data cutoff of November 19, 2024. In the pivotal cohort of the ADVANCED-2 trial in BCG-Unresponsive patients, the CR rate was 100% (4/4) at six-months and 80% (4/5) at any time. In the proof-of-concept cohort of BCG-Naïve patients, the CR rate was 64% (9/14) at six months and 67% (10/15) at any time. TARA-002 demonstrated a favorable safety and tolerability profile with no Grade 2 or greater treatment-related adverse events (TRAEs), and no patients discontinued due to adverse events.

"These impressive TARA-002 results demonstrate meaningful activity in a difficult to treat patient population," said Brian Mazzarella, MD, Vice President of Research for Urology America, and ADVANCED-2 study investigator. "The activity of TARA-002 across BCG exposures, coupled with its ease of use and low procedural burden for physicians, make it an exciting potential treatment option for NMIBC patients."

"We are thrilled with these positive six-month data, which reinforce TARA-002’s potential in NMIBC, while offering a compelling product profile for physicians and patients," said Jesse Shefferman, Chief Executive Officer of Protara Therapeutics. "We believe these encouraging data together with our international site expansion will accelerate patient enrollment, and we look forward to reporting initial data from 12-month evaluable patients in mid-2025."

The majority of adverse events were Grade 1 and transient with no Grade 2 or greater TRAEs as assessed by study investigators. No patients discontinued treatment due to adverse events. The most common adverse events were in line with typical responses to bacterial immunopotentiation, such as flu-like symptoms. The most common urinary symptoms reflect urinary tract instrumentation effects, such as bladder spasm, burning sensation, and urinary tract infection. Most bladder irritations resolved shortly after administration or within a few hours to a few days.

Conference Call and Webcast

Protara will host a conference call and webcast to discuss the data today at 8:30 am ET. The live call can be accessed by registering as a participant here. Upon registration, participants will receive conference call dial-in information. A live webcast of the event can be accessed by visiting the Events and Presentations section of the Company’s website: View Source The webcast will be archived for a limited time following the presentation.

About ADVANCED-2

The Phase 2 open-label ADVANCED-2 trial is assessing intravesical TARA-002 in NMIBC patients with carcinoma in situ or CIS (± Ta/T1) who are Bacillus Calmette-Guérin (BCG)-Unresponsive (n≈100) and BCG-Naïve (n=27). The BCG-Unresponsive cohort has been designed to be registrational in alignment with the FDA’s 2024 BCG-Unresponsive Non-muscle Invasive Bladder Cancer: Developing Drugs and Biological Products for Treatment Draft Guidance for Industry.

About TARA-002

TARA-002 is an investigational cell therapy in development for the treatment of NMIBC and of LMs, for which it has been granted Rare Pediatric Disease Designation by the U.S. Food and Drug Administration. TARA-002 was developed from the same master cell bank of genetically distinct group A Streptococcus pyogenes as OK-432, a broad immunopotentiator marketed as Picibanil in Japan and approved in Taiwan by Chugai Pharmaceutical Co., Ltd. Protara has successfully shown manufacturing comparability between TARA-002 and OK-432.

When TARA-002 is administered, it is hypothesized that innate and adaptive immune cells within the cyst or tumor are activated and produce a pro-inflammatory response with release of cytokines such as tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, IL-1b, IL-6, IL-12, granulocyte-macrophage colony-stimulating factor (GM-CSF) and natural killer cells. TARA-002 also directly kills tumor cells and triggers a host immune response by inducing immunogenic cell death, which further enhances the antitumor immune response.

About Non-Muscle Invasive Bladder Cancer (NMIBC)

Bladder cancer is the sixth most common cancer in the United States, with NMIBC representing approximately 80% of bladder cancer diagnoses. Approximately 65,000 patients are diagnosed with NMIBC in the United States each year. NMIBC is cancer found in the tissue that lines the inner surface of the bladder that has not spread into the bladder muscle.

On December 5, 2024 UroGen Pharma Ltd. (Nasdaq: URGN), a biotech company dedicated to developing and commercializing innovative solutions that treat urothelial and specialty cancers, reported results from a long-term follow-up study with JELMYTO (mitomycin) for pyelocalyceal solution, which is FDA approved for the treatment of adults with low-grade, upper tract urothelial cancer (LG-UTUC) (Press release, UroGen Pharma, DEC 5, 2024, View Source [SID1234648835]). Among patients from the OLYMPUS trial who achieved a complete response after primary chemoablation with JELMYTO (n=41, 20 of whom entered the long-term follow-up study), the median duration of response was 47.8 months (median follow-up 28.1 months (95% CI 13.1, 57.5). The study results were presented at the Society for Urologic Oncology (SUO) annual meeting in Dallas, Texas, and were recently published online in the Journal of Urology.

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"The median duration of response of 47.8 months in patients who achieved a complete response with JELMYTO demonstrates robust long-term control of LG- UTUC," said Brian Hu, M.D., Associate Professor of Urology, Loma Linda University School of Medicine and study investigator. "With these compelling data showing sustained complete response, JELMYTO provides a valuable treatment option for potentially achieving a long-lasting recurrence-free interval."

Of the 71 patients enrolled in OLYMPUS, 41 achieved a complete response after treatment with JELMYTO and had a median duration of response of 47.8 months (95% CI 13.0, not estimable), with median follow-up of 28.1 months (95% CI 13.1, 57.5).

"Managing relapse and preserving kidney function are key treatment goals for LG-UTUC, as the risk of disease progression is low," said Mark Schoenberg, M.D., Chief Medical officer, UroGen. "The study’s findings are compelling, as they support the potential of JELMYTO to offer patients long-lasting benefits, with evidence of an extended response duration that may improve quality of life and reduce the need for more invasive treatments."

The analysis has certain limitations, including its post-hoc nature and the inherent selection bias of the 20 patients enrolled in the long-term follow-up study.

About JELMYTO

JELMYTO (mitomycin) for pyelocalyceal solution is a mitomycin-containing reverse thermal gel containing 4 mg mitomycin per mL gel approved for the treatment of adult patients with low-grade-UTUC (LG-UTUC). 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 a 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.

About Upper Tract Urothelial Cancer (UTUC)

Urothelial cancer is the ninth most common cancer globally and the eighth most lethal neoplasm in men in the U.S. Between five percent and ten percent of primary urothelial cancers originate in the ureter or renal pelvis and are collectively referred to as UTUC. In the U.S., there are approximately 6,000 – 7,000 new or recurrent LG-UTUC patients annually. Most cases are diagnosed in patients over 70 years old, and these older patients often have multiple comorbidities. There are limited treatment options for UTUC, with the most common being endoscopic surgery or nephroureterectomy (removal of the entire kidney and ureter). Treatment with endoscopic surgery can be associated with a high rate of recurrence and relapse.