On May 4, 2024 UroGen Pharma Ltd. (Nasdaq: URGN), a biotech company dedicated to developing and commercializing novel solutions that treat urothelial and specialty cancers, reported the results of a sub-analysis from a real-world patient cohort review of JELMYTO (mitomycin) for pyelocalyceal solution presented at the American Urological Association Meeting 2024 in San Antonio, TX (Press release, UroGen Pharma, MAY 4, 2024, View Source [SID1234642644]). The study includes a stepwise approach to retrograde administration of JELMYTO and reports that retrograde administration of JELMYTO in the clinic (n=20) produced a 60% complete response rate in patients and ureteral stents were placed in 25% of patients, which is lower than the rate reported in the pivotal OLYMPUS study.

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"The retrograde instillation of JELMYTO for the clinical management of low-grade upper tract urothelial cancer is FDA-approved and offers a safe and efficacious mode of administration, and this study in a real-world population adds to the growing body of evidence supporting retrograde administration in appropriate patients," said Khurshid Ridwan Ghani, MBChB, MS, FRCS, Professor of Urology, Director, Michigan Urological Surgery Improvement Collaborative. "The stepwise approach outlined in this study offers valuable insights into achieving positive efficacy and safety outcomes, in the clinic with the procedure done under local anesthesia, with notable durability of response observed."

In the OLYMPUS study all enrolled patients (n=71) received retrograde administration of JELMYTO. In the OLYMPUS study 58% (n=41) of patients achieved a complete response, defined as the absence of tumor lesions 3 months after initiation of JELMYTO treatment assessed by urine cytology and ureteroscopy. Ureteric obstruction* was reported in 58% (n=41) of patients treated with JELMYTO and 88% (n=36) of that subgroup went on to receive ureteral stent placement. For additional information about the retrograde administration of JELMYTO, consult the JELMYTO Instructions for Administration accompanying the Full Prescribing Information.

In this retrospective real-world study, 20 patients with a mean tumor burden of 1.67 cm received at least one dose of JELMYTO via the retrograde mode of administration, of which 16 (80%) completed six instillations. Twelve patients (60%) had a complete response and seven patients (35%) received at least one dose of monthly maintenance therapy, of which five demonstrated durability of response (4 patients remained tumor-free at 14.25-month follow-up and 1 patient at 24 months). Six patients (30%) had an adverse event related to the urinary system. Ureteral stents were placed in five patients for stenosis (25%); of which four were transient, with no subsequent obstruction. Only one patient (5%) required permanent stenting. Three patients who were unable to tolerate the retrograde approach had antegrade administration of JELMYTO via a nephrostomy tube.

"These findings emphasize the versatility of JELMYTO administration and also underscore the significance of continuous research and innovation in elevating treatment standards for urothelial cancers," remarked Mark Schoenberg, M.D., Chief Medical Officer at UroGen.

The limitations of this sub-analysis include the small sample size, the retrospective design, lack of a control group, and the lack of a centralized pathology review and standardized clinicopathologic assessment.

To further explore the full potential of JELMYTO for the treatment of patients with upper tract urothelial cancers (UTUC), investigators are in the process of enrolling the prospective and retrospective uTRACT Registry to capture data in a large-scale, standardized manner to report further on patient outcomes following JELMYTO treatment including longitudinal follow-up.

*Includes hydronephrosis, obstructive uropathy, pelvic-ureteric obstruction, ureteric obstruction, ureteric stenosis, and urinary tract obstruction.

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 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 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 face comorbidities. There are limited treatment options for UTUC, with the most common being endoscopic surgery or nephroureterectomy (removal of the entire kidney and ureter). These treatments can lead to a high rate of recurrence and relapse.

On May 3, 2024 Xspray Pharma reported the company determined the outcome of exercised warrants of series TO6, issued in connection with the rights issue in June 2023 and for which the subscription period ended on May 2, 2024 (Press release, Xspray, MAY 3, 2024, View Source [SID1234650112]). In total, 2,508,723 series TO6-warrants were exercised to subscribe for the same amount of new shares. Xspray Pharma thereby receives proceeds of SEK 100.3 million before transaction costs. Proceeds will be used for the US launch of the company’s first product, Dasynoc, as well as for continued development of other product candidates in the company’s portfolio.

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"I’m pleased that our shareholders demonstrate their support for Xspray Pharma to an even greater degree than in our previous warrant program, by subscribing newly issued shares and thereby contribute with additional capital towards our commercialization plan. These funds will enable a successful launch of our first product Dasynoc on September 1 this year," comments Per Andersson, CEO of Xspray Pharma.

In connection to the rights issue completed in June 2023, 3,132,946 warrants of series TO6 were issued. Each TO6 gave the right to subscribe for a newly issued share for SEK 40 during the period 16 April – 2 May 2023. When the subscription period had ended, 2,508,723 TO6-warrants had been used to subscribe for shares at SEK 40 each, corresponding to 80% of the warrants. The number of shares in the company thereby increases by 2,508,723 and the share capital increases by SEK 2,508,723 SEK.

The proceeds raised by the exercise of warrants of series TO6 will primarily be used to fund the launch of Dasynoc on the US market which is planned for September 1 this year subject to approval by FDA. Proceeds will also be used for general operational purposes, ongoing operational costs and continued development of product candidates. Xspray Pharma currently has four announced product candidates based on the company’s patented HyNap-technology.

On May 3, 2024 FoRx Therapeutics AG, a company committed to discovering and developing innovative drugs targeting cancer-relevant DNA Damage Response (DDR) pathways, reported the nomination of its first preclinical development candidate, FORX-428, an inhibitor of Poly(ADP-ribose) glycohydrolase (PARG) (Press release, FoRx Therapeutics, MAY 3, 2024, View Source [SID1234644973]). FORX-428 has strong best-in-class potential and is being developed for the treatment of solid tumors. IND-enabling activities have already been initiated.

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FORX-428 is an oral, highly potent and selective inhibitor of PARG that shows excellent single-agent activity in multiple relevant preclinical tumor models. The compound is well tolerated and demonstrates a favorable pharmacological and safety profile. In addition to single-agent activity resulting in tumor regressions, FORX-428 exhibits synergistic tumor cell killing in combination with various targeted agents, underscoring the compound’s outstanding potential in both monotherapy and combination settings to address genetically defined cancers. FoRx Therapeutics has identified novel predictive biomarkers which allow for the selection of patient populations most likely to benefit from treatment. FORX-428 has the potential to achieve transformative outcomes in patients with cancers of high medical need or affected by therapy resistance.

FoRx Therapeutics holds all development and commercial rights to FORX-428.

Dr Tarig Bashir, CEO of FoRx Therapeutics, commented: "We are proud to announce the nomination of our first development candidate FORX-428. The achievement of this important milestone is a testimony to FoRx Therapeutics’ ability to tackle and successfully deliver on challenging targets in the DNA Damage Response field. We look forward to advancing FORX-428 with its best-in-class profile into the clinic and to bring a novel treatment option with transformative potential to cancer patients who have at this point only limited therapy options or suffer from therapy resistance."

Dr Frank Zenke, CSO of FoRx Therapeutics, added: Our dedicated research team has achieved a remarkable milestone, conducting an extensive investigation of various chemical series aimed at identifying a development candidate with best-in-class potential. FORX-428 exhibits compelling anti-tumor efficacy and exceptional tolerability in numerous cancer models, and we are excited to advance this promising compound into clinical trials for cancer patients."

About PARG
Poly(ADP-ribose) glycohydrolase (PARG) is a key protein that plays a pivotal role in repairing damaged DNA. PARG breaks down poly(ADP-ribose) (PAR) chains, which serve to attract DNA repair factors to sites of DNA damage. Cancers are by default genomically instable and cannot tolerate excessive DNA damage as opposed to normal cells. By inhibiting PARG, the degradation of PAR chains is halted, leading to a block of DNA repair and the accumulation of persistent and lethal DNA damage. Cancers with intrinsic deficiencies in particular DNA repair pathways exhibit exceptional sensitivity to pharmacological PARG inhibition, which presents a prime opportunity for therapeutic intervention.

On May 3, 2024 Natera, Inc. (NASDAQ: NTRA), a global leader in cell-free DNA and genetic testing, reported a new publication in JCO Precision Oncology reporting on the ability of its personalized and tumor-informed molecular residual disease (MRD) test, Signatera, to detect recurrence early in patients with early-stage breast cancer (Press release, Natera, MAY 3, 2024, View Source [SID1234642642]). The full study can be found here.

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The study evaluated a total of 1,136 prospectively collected and banked plasma samples from 156 early-stage breast cancer patients enrolled in the multi-site Exploratory Breast Lead Interval Study (EBLIS). Patients were followed for up to 12 years after surgery and adjuvant chemotherapy, with blood samples collected semi-annually and then analyzed using Signatera. Key findings include:

Signatera detected relapse up to 38 months earlier than imaging (median lead time 10.5 months), with an overall sensitivity of 88.2% (30/34)
Relapse-free survival (RFS) and overall survival (OS) were significantly worse in patients who were ctDNA-positive, regardless of hormone receptor and HER2 subtype (HR 52.98 and 53.69, respectively). In a multivariate analysis, ctDNA status was the most significant factor associated with RFS and OS.
"The EBLIS study shows that post-operative monitoring with Signatera can detect recurrence much earlier than scans, opening up a critical window for early therapeutic intervention and clinical trials focused on molecular recurrence," said Charles Coombes, MD, PhD professor of medical oncology at the Imperial College London and principal investigator of the EBLIS study. "Additionally, we demonstrate the value of longitudinal testing in providing reassurance to breast cancer patients, as those who test serially ctDNA-negative show better clinical outcomes."

Breast cancer is the most common cancer in women in the U.S. and the second leading cause of cancer death in women.1 The current standard of care for most patients with early-stage breast cancer consists of surgery and adjuvant chemotherapy and/or endocrine therapy.2,3 However, patients with early-stage breast cancer experience a rate of local recurrence of roughly 15% and distant metastases of 21% after primary treatment.4

"This expanded EBLIS study reinforces the importance of early recurrence detection with Signatera and the potential to improve care management for patients with breast cancer," said Minetta Liu, MD, chief medical officer of oncology. "The findings also bolster the evidence for long-term monitoring of high-risk breast cancer patients, who often face late recurrences."

About Signatera

Signatera is a personalized, tumor-informed, molecular residual disease test for patients previously diagnosed with cancer. Custom-built for each individual, Signatera uses circulating tumor DNA to detect and quantify cancer left in the body, identify recurrence earlier than standard of care tools, and help optimize treatment decisions. The test is available for clinical and research use and is covered by Medicare for patients with colorectal cancer, breast cancer, ovarian cancer and muscle invasive bladder cancer, as well as for immunotherapy monitoring of any solid tumor. Signatera has been clinically validated across multiple cancer types and indications, with published evidence in more than 60 peer-reviewed papers.

On May 3, 2024 Castle Biosciences, Inc. (Nasdaq: CSTL), a company improving health through innovative tests that guide patient care, reported that new data supporting the utility of its DecisionDx-SCC test in patients with high-risk cutaneous squamous cell carcinoma (SCC) tumors located on the head and neck (H&N) will be shared at the 56th American College of Mohs Surgery (ACMS) Annual Meeting, being held May 2-5 in Phoenix (Press release, Castle Biosciences, MAY 3, 2024, View Source [SID1234642641]).

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"Mohs surgery is commonly used to remove high-risk SCC tumors located on a patient’s head or neck and is the best method to ensure complete removal of the tumor," said Sherrif Ibrahim, M.D., Ph.D., lead study author and board-certified Mohs micrographic surgeon and dermatologist at Rochester Dermatologic Surgery in Victor, New York. "In most cases, once a tumor is removed completely, the patient is in the clear. However, aggressive SCC tumors may still return in the same location from which they were removed or worse, spread to other parts of the body, posing a very serious health risk to patients.

"The data being presented at ACMS show the power of DecisionDx-SCC to identify these high-risk patients, enabling more risk-appropriate surveillance or adjuvant treatments to help reduce the patient’s risk of these events occurring."

Details regarding Castle’s poster at ACMS are included below:

Title: Addition of the 40-gene expression profile (40-GEP) test in risk assessment improves prognostic accuracy and risk stratification for high-risk cutaneous squamous cell carcinoma (HR-cSCC) of the head and neck successfully treated with Mohs micrographic surgery (MMS)
Poster Number: Poster 21
First and Presenting Author: Sherrif Ibrahim, M.D., Ph.D.
Location: Valley of the Sun Ballroom foyer (2nd floor), Sheraton Phoenix Downtown
Summary: Despite reported definitive, clear tumor margins, 5-8% of patients with high-risk SCC treated with Mohs surgery will still develop metastasis. This study included 417 patients who received definitive Mohs surgery to remove high-risk SCC tumors of the H&N with reported clear margins. DecisionDx-SCC testing of the tumor tissue before removal significantly increased the prediction accuracy of metastatic events, when used alone and when combined with National Comprehensive Cancer Network (NCCN) guidelines, Brigham and Women’s Hospital (BWH) staging or American Joint Committee on Cancer Staging Manual, 8th Edition (AJCC8) staging, to better guide risk-aligned patient care decisions regarding metastatic surveillance or the use of adjuvant treatments like radiation.
Presenting authors will be available to answer questions regarding their posters on Saturday, May 4, from 12-1 p.m. Mountain Standard Time. Abstracts will also be in ACMS’ CME & Abstract Book and available for online viewing via the Planstone abstract site.

About DecisionDx-SCC

DecisionDx-SCC is a 40-gene expression profile test that uses an individual patient’s tumor biology to predict individual risk of cutaneous squamous cell carcinoma metastasis for patients with one or more risk factors. The test result, in which patients are stratified into a Class 1 (low), Class 2A (higher) or Class 2B (highest) risk category, predicts individual metastatic risk to inform risk-appropriate management. Peer-reviewed publications have demonstrated that DecisionDx-SCC is an independent predictor of metastatic risk and that integrating DecisionDx-SCC with current prognostic methods can add positive predictive value to clinician decisions regarding staging and management.