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.

On May 3, 2024 Johnson & Johnson reported updated results from Cohort 2 of the Phase 2b SunRISe-1 study evaluating the efficacy and safety of investigational TAR-200 monotherapy in patients with BCG-unresponsive high-risk non–muscle-invasive bladder cancer (HR-NMIBC) with carcinoma in situ, who are ineligible for, or decline, radical cystectomy (Press release, Johnson & Johnson, MAY 3, 2024, View Source [SID1234642640]). These data were featured today in a plenary session (Abstract #P2-01) at the 2024 American Urological Association Annual Meeting (AUA) taking place May 3-6, 2024, in San Antonio, Texas.

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"The high complete response rate and durability of these responses observed in patients treated with TAR-200 underscores the potential of this treatment approach for patients with BCG-unresponsive HR-NMIBC," said Joseph Jacob,* M.D., M.S., Department of Urology, Upstate Medical University, presenting author. "These results address an area of high unmet need for bladder sparing therapies in this patient population."

Results included an evaluation of 85 patients (median age of 71 years old: range 40-88; 32.9% with concurrent papillary disease) who received TAR-200 monotherapy. The centrally confirmed complete response (CR) rate was 82.8% by urine cytology and/or biopsy (95% confidence interval [CI], 70.6-91.4). The study protocol did not allow retreatment for nonresponders, consistent with U.S. Food and Drug Administration (FDA) guidance. The estimated 1-year duration of response (DOR) rate is 74.6% (95% CI, 49.8-88.4), with median follow-up in responders of 29.9 weeks (range, 14-140); 41 of 48 responders (85%) remain in CR at data cutoff as of January 2, 2024, and none of the responders progressed to muscle-invasive bladder cancer or metastasis. Ninety-eight percent (47 of 48) of CRs were achieved at first disease assessment at week 12, and four of five patients who have completed two years of treatment remain in CR. The investigator-assessed confirmed CR rate correlated strongly with central results.1

Interim results from the SunRISe-1 study were featured at the European Society for Medical Oncology 2023 Congress and shared at AUA 2023. These results were also presented at the European Association of Urology 2024 Congress.

Treatment-related adverse events (TRAEs) occurred in 61 patients (71.8%). The most common (≥10%) were pollakiuria (35.3%), dysuria (29.4%), micturition urgency (15.3%), and urinary tract infections (15.3%). Seven patients (8.2%) had Grade 3 or higher TRAEs and four patients (4.7%) had one or more serious TRAEs. Four patients (4.7%) had TRAEs leading to discontinuation and no deaths were reported.

"These study results mark a significant step in our mission to bring new treatment options to patients that focus on bladder preservation and long-term survival," said Christopher Cutie, M.D., Vice President, Disease Area Leader, Bladder Cancer, Johnson & Johnson Innovative Medicine. "These results reinforce the potential of TAR-200 to transform the treatment landscape and our ongoing dedication to address unmet needs for patients facing this challenging disease."

TAR-200 is an investigational targeted releasing system designed to provide extended local release of gemcitabine into the bladder. It is installed in a physician’s office setting during a 3- to 5-minute procedure with no anesthesia. In December 2023, the FDA granted TAR-200 Breakthrough Therapy Designation (BTD) for the potential future treatment of patients with BCG-unresponsive HR-NMIBC, who are ineligible for or elected not to undergo radical cystectomy (surgical removal of the bladder).

Bladder cancer is the sixth most common cancer in the U.S., with more than 83,000 patients diagnosed each year, with NMIBC accounting for about 75-85% of all newly diagnosed bladder cancers.2,3 Although BCG immunotherapy has been accepted as the standard of care for nearly five decades, 30-40% of patients do not respond to BCG and experience disease recurrence or progression.4 In such scenarios, radical cystectomy (removal of the bladder and neighboring structures and organs) emerges as the primary treatment option. This major abdominal procedure requires a urinary diversion to be created to collect and store urine.5

About SunRISe-1
SunRISe-1 (NCT04640623) is a randomized, parallel-assignment, open-label Phase 2 clinical study evaluating the safety and efficacy of TAR-200 in combination with cetrelimab, TAR-200 alone, or cetrelimab alone for BCG-unresponsive HR-NMIBC carcinoma in situ (CIS) patients who are ineligible for, or elected not to undergo, radical cystectomy. Participants are randomized to 1 of 4 cohorts: treatment with TAR-200 in combination with cetrelimab (Cohort 1), TAR-200 alone (Cohort 2), cetrelimab alone (Cohort 3), or TAR-200 alone with papillary disease only (Cohort 4). The primary endpoint is CR rate at any time point. Secondary endpoints include DOR, overall survival, pharmacokinetics, quality of life, safety and tolerability. Cohorts 1 and 3 were closed to further enrollment effective June 1, 2023.

About TAR-200
TAR-200 is an investigational targeted releasing system, enabling controlled release of gemcitabine into the bladder, increasing the amount of time the drug delivery system spends in the bladder and sustaining local drug exposure. The safety and efficacy of TAR-200 are being evaluated in Phase 2 and Phase 3 studies in patients with muscle-invasive bladder cancer in SunRISe-2 and SunRISe-4, NMIBC in SunRISe-1, SunRISe-3 and SunRISe-5.

About Cetrelimab
Administered intravenously, cetrelimab is an investigational programmed cell death receptor-1 (PD-1) monoclonal antibody being studied for the treatment of bladder cancer, prostate cancer, melanoma, and multiple myeloma as part of a combination treatment. Cetrelimab is also being evaluated in multiple other combination regimens across the Janssen Oncology portfolio.

About High-Risk Non–Muscle-Invasive Bladder Cancer
High-risk non–muscle-invasive bladder cancer (HR-NMIBC) is a type of non-invasive bladder cancer that is more likely to recur or spread beyond the lining of the bladder, called the urothelium, and progress to invasive bladder cancer compared to low-risk NMIBC.6,7 HR-NMIBC makes up 15-44% of patients with NMIBC and is characterized by a high-grade, large tumor size, presence of multiple tumors, and CIS. Radical cystectomy is currently recommended for NMIBC patients who fail BCG therapy, with over 90% cancer-specific survival if performed before muscle-invasive progression.8,9 Given that NMIBC typically affects older patients, many may be unwilling or unfit to undergo radical cystectomy.10 The high rates of recurrence and progression can pose significant morbidity and distress for these patients.