On December 5, 2024 Theriva Biologics (NYSE American: TOVX), a diversified clinical-stage company developing therapeutics designed to treat cancer and related diseases in areas of high unmet need, reported the outcomes of a recent Type D meeting with the U.S. Food and Drug Administration (FDA) to obtain guidance on the design of a Phase 3 clinical study of lead clinical candidate VCN-01 in combination with standard-of-care chemotherapy for the treatment of metastatic pancreatic adenocarcinoma (PDAC) (Press release, Theriva Biologics, DEC 5, 2024, View Source [SID1234648836]). The Company recently announced the completion of target enrollment into the multinational VIRAGE Phase 2b clinical study evaluating intravenous VCN-01 in combination with gemcitabine/nab-paclitaxel as a first line therapy for PDAC patients.

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Type D meetings are focused on a narrow set of issues that are used to discuss issues at key decision points to provide timely feedback critical to moving a drug development program forward. The FDA advised that the on-going VIRAGE Phase 2b study should not be expanded into a Phase 3 study; rather, the optimal path forward for the VCN-01 PDAC program is to conduct a stand-alone Phase 3 study of VCN-01 with gemcitabine/nab-paclitaxel. The FDA provided general agreement with Theriva’s proposed design for a Phase 3 clinical study and indicated that inclusion of additional standard-of-care chemotherapy for PDAC was not necessary as it would complicate the study design and analysis. The FDA meeting also highlighted the FDA’s preferences regarding certain statistical elements of confirmatory clinical studies, including methods for sample size estimation and the study population(s) used for data analysis.

"The FDA’s advice on key elements of a potential confirmatory Phase 3 study evaluating VCN-01 plus gemcitabine/nab-paclitaxel as a first-line treatment for metastatic PDAC patients is critical as the VIRAGE study has entered final patient follow-up and we are actively planning the next steps in VCN-01 development," said Steven A. Shallcross, Chief Executive Officer of Theriva Biologics. "The feedback from the FDA and European regulatory agencies will facilitate the design of a Phase 3 study protocol that is expected to maximize our ability to provide a new therapeutic option to patients suffering this terrible disease."

An additional meeting with the FDA will be requested after the completion of the VIRAGE study to discuss the details of the proposed confirmatory Phase 3 study protocol.

About Pancreatic Ductal Adenocarcinoma

Cancer of the pancreas consists of two main histological types: cancer that arises from the ductal (exocrine) cells of the pancreas or, much less often, cancers may arise from the endocrine compartment of the pancreas. Pancreatic ductal adenocarcinoma ("PDAC") accounts for more than 90% of all pancreatic tumors. It can be located either in the head of the pancreas or in the body/tail. Pancreatic cancer usually metastasizes to the liver and peritoneum. Other less common metastatic sites are the lungs, brain, kidney, and bone. In its early stages, pancreatic cancer does not typically result in any characteristic symptoms. In many instances, progressive abdominal pain is the first symptom. Therefore, in most cases, pancreatic cancer is diagnosed in its late stages (locally advanced non-metastatic or metastatic stage of the disease) when surgical resection and possibly curative treatment is not possible. It is generally assumed that only 10% of cases are resectable at presentation, whereas 30-40% of patients are diagnosed at local advanced/unresectable stage and 50-60% present with distant metastases.

About VCN-01

VCN-01 is a systemically administered oncolytic adenovirus designed to selectively and aggressively replicate within tumor cells and degrade the tumor stroma that serves as a significant physical and immunosuppressive barrier to cancer treatment. This unique mode-of-action enables VCN-01 to exert multiple antitumor effects by (i) selectively infecting and lysing tumor cells; (ii) enhancing the access and perfusion of co-administered chemotherapy products; and (iii) increasing tumor immunogenicity and exposing the tumor to the patient’s immune system and co-administered immunotherapy products. Systemic administration enables VCN-01 to exert its actions on both the primary tumor and metastases. VCN-01 has been administered to 142 patients to date in Company- and investigator-sponsored clinical trials of different cancers, including PDAC (in combination with chemotherapy), head and neck squamous cell carcinoma (with an immune checkpoint inhibitor), ovarian cancer (with CAR-T cell therapy), colorectal cancer, and retinoblastoma (by intravitreal injection). More information on these clinical trials is available at Clinicaltrials.gov.

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.

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 Revolution Medicines, Inc. (Nasdaq: RVMD), a clinical-stage oncology company developing targeted therapies for patients with RAS-addicted cancers, reported the closing of its underwritten public offering of 16,576,088 shares of its common stock at a public offering price of $46.00 per share, before underwriting discounts and commissions, and, in lieu of shares of common stock, to certain investors, pre-funded warrants to purchase 2,173,917 shares of common stock at a public offering price of $45.9999, which represents the per share public offering price for the common stock less the $0.0001 per share exercise price for each pre-funded warrant (Press release, Revolution Medicines, DEC 5, 2024, View Source [SID1234648833]). The shares of common stock issued and sold in the offering include 2,445,652 shares issued upon exercise in full by the underwriters of their option to purchase additional shares of common stock at the public offering price, less underwriting discounts and commissions. The gross proceeds from the offering, before deducting underwriting discounts and commissions and other offering expenses payable by Revolution Medicines, were $862.5 million. All shares and pre-funded warrants in the offering were offered by Revolution Medicines.

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J.P. Morgan, TD Cowen, Goldman Sachs & Co. LLC and Guggenheim Securities acted as joint book-running managers for the offering. UBS Investment Bank acted as lead manager.

A shelf registration statement relating to these securities was filed with the U.S. Securities and Exchange Commission (SEC) on March 4, 2024, and automatically became effective upon filing. This offering was made solely by means of a prospectus. A copy of the final prospectus supplement and the accompanying prospectus relating to this offering may be obtained for free by visiting EDGAR on the SEC’s website at www.sec.gov. Alternatively, a copy of the final prospectus supplement and the accompanying prospectus relating to this offering may be obtained by contacting: J.P. Morgan Securities LLC, Attention: Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, New York 11717, by email at [email protected] and [email protected]; TD Securities (USA) LLC, 1 Vanderbilt Avenue, New York, New York 10017, by telephone at (855) 495-9846 or by email at [email protected]; Goldman Sachs & Co. LLC, Attention: Prospectus Department, 200 West Street, New York, NY 10282, by telephone at (866) 471-2526 or by email at [email protected]; and Guggenheim Securities, LLC, Attention: Equity Syndicate Department, 330 Madison Avenue, 8th Floor, New York, New York 10017, by telephone at (212) 518-9544 or by email at [email protected].

This press release shall not constitute an offer to sell or a solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction.

On December 5, 2024 Xenetic Biosciences, Inc. (NASDAQ:XBIO) ("Xenetic" or the "Company"), a biopharmaceutical company focused on advancing innovative immuno-oncology technologies addressing hard to treat cancers, reported it has entered into a Clinical Trial Services Agreement (the "Agreement") with the Israel-based biotechnology company PeriNess Ltd. ("PeriNess") to advance the Company’s development program for its systemic DNase I candidate in combination with chemotherapy and immunotherapy platforms for the treatment of pancreatic carcinoma, colorectal cancer and other locally advanced or metastatic solid tumors toward exploratory clinical studies (Press release, Xenetic Biosciences, DEC 5, 2024, View Source [SID1234648832]).

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"We are pleased to be working with PeriNess, and to have the opportunity to leverage their experience for the development of Xenetic’s intravenous DNase I candidate through preclinical and early-stage clinical programs. We are excited to take this step forward on the path to the clinic and look forward to investigating our systemic DNase I candidate, XBIO-015, as an adjunctive treatment," commented James Parslow, Interim Chief Executive Officer and Chief Financial Officer of Xenetic.

"We are thrilled to enter this strategic Clinical Trial Services Agreement with Xenetic and further advance the development of their systemic DNase I platform. We believe this collaboration is a great example of where we can put substantial synergies from our projects toward accelerating the clinical development of a highly promising DNase I program for patients in need of new therapies," commented Michal Ben Attar, Chief Executive Officer of PeriNess.

A large body of published preclinical data highlights the pivotal role of Neutrophil Extracellular Traps (NETs) in modulating cancer chemotherapy and immunotherapy efficacy and provides a strong rationale for incorporating DNase I as an adjunctive treatment to improve therapeutic responses in patients with pancreatic and colorectal cancers receiving chemotherapy and immunotherapy.

Under the terms of the Agreement, PeriNess will lead in the regulatory approval, operational execution and management of potential exploratory, investigator initiated studies of recombinant DNase as an adjunctive treatment in patients with pancreatic carcinoma and other locally advanced or metastatic solid tumors receiving chemotherapy and immunotherapy in Israeli medical centers.