On January 15, 2025 XENOTHERA reported the launch of two new dose cohorts in its oncology clinical trials (Press release, Xenothera, JAN 15, 2025, View Source [SID1234649744]). The biotech announces the fifth dose cohort (16mg) in the FIPO trial, which is testing XON7 in patients with solid tumors, and the second dose cohort (4mg) in the PALT trial, which is testing LIS22 in peripheral T-cell lymphoma (PTCL). These results indicate that the biotech’s anti-cancer antibodies are well tolerated, and mark major milestones in its development.

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Since 2019, XENOTHERA has been extending its expertise to the development of antibodies against cancer, in addition to its initial positioning in transplantation. Its innovative glyco-humanized polyclonal antibody (GH-pAb) technology offers promising prospects by killing cancer cells, blocking tumor escape mechanisms, limiting metastasis and combining several actions to fight cancers effectively (see publication by Ciron et al. 2024).

XENOTHERA is currently conducting clinical trials with two antibodies designed to combat cancer. XON7 is a GH-pAb that targets an original combination of tumor markers and induces a modification of the tumor environment. In vivo, XON7 has superior activity to chemotherapy in several types of cancer. The FIPO trial (NCT06154291) is a phase I/II trial testing XON7 in patients with various solid tumors (according to the protocol, sarcoma, triple-negative breast, colorectal, lung, gastro-esophageal, pancreas, ovary). Following the 1.5mg, 3mg, 6mg and 12mg dose cohorts, XENOTHERA has announced the start of the 16mg dose cohort, which has been validated by the trial’s Scientific Advisory Board. Three patients have already received this new dose. A final dose of 20mg is planned in the trial design before moving on to phase II.

LIS22 is a GH-pAb designed to specifically target mature tumour lymphocytes responsible for certain aggressive lymphomas (PTCL). It has been granted orphan drug status by the FDA and the EMA and is in phase I/II (PALT1 trial, NCT06495723) since July 2024 in PTCL patients. Following an initial patient treated at 2mg, the trial’s Scientific Advisory Board approved the switch to a 4mg dose. Three patients are currently being treated at 4mg, and will be followed by 6 patients at 6mg. The PALT trial is being supported in the France 2030 programme, with a 4M€ funding recently announced by the biotech company.

"These important milestones document the safety of our antibodies, which is per se a major asset in the treatment of cancer, where too many drugs induce harmful side-effects for patients. We are now reaching dose levels where we can expect the first signs of efficacy, even if this is not the intention at this stage, when we are focusing on safety. Basically, we are confident because the in vivo scientific data are very convincing, and we hope that patients will be the first to benefit from our advances. More fundamentally, this is a clear sign that our technology represents an avenue of innovation in oncology, and we are very proud of this. I would like to take this opportunity to thank the patients, the medical teams and the entire XENOTHERA team for their involvement in these major clinical trials’, comments Odile Duvaux, Chairman of the company.

On January 15, 2025 XENOTHERA reported the securing of a €4 million financing from the public investment program France 2030 to develop its PALT24 project (Polyspecific Antibodies in Lymphoproliferative T cell disorders) (Press release, Xenothera, JAN 15, 2025, View Source [SID1234649743]). This project aims a particularly agressive onco-hematologic disease with high unmet medical needs : PTCL, as the five year survival rate remains at only 30%.

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This financing will enable us to launch the PALT1 clinical trial and pursue early access authorization in France and Europe by 2027. XENOTHERA’s polyclonal glyco-humanized antibody (GH-pAb) is unique in its ability to target tumor cells selectively without affecting healthy lymphocytes, a major advancement in PTCL treatment. Already recognized as an "orphan drug" by both the FDA and EMA, it brings unprecedented hope for patients.

On January 15, 2025 UroGen Pharma Ltd. (Nasdaq: URGN), a biotech company dedicated to developing and commercializing innovative solutions that treat urothelial and specialty cancers, reported that the 3-month complete response (CR) rate and 12-month durability of response from the Phase 3 ENVISION study of investigational drug UGN-102 in patients with low-grade intermediate-risk non-muscle-invasive bladder cancer (LG-IR-NMIBC) were published in the February issue of The Journal of Urology (Press release, UroGen Pharma, JAN 15, 2025, View Source [SID1234649742]).

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In the ENVISION trial, UGN-102 treatment demonstrated an impressive 82.3% (95% CI, 75.9%, 87.1%) 12-month duration of response (DOR) by Kaplan-Meier estimate (n=108) in patients who achieved a CR at three months after the first instillation of UGN-102 (mitomycin) for intravesical solution. The Kaplan-Meier estimates for DOR at 15 months (n=43) and 18 months (n=9) following the 3-month CR were both 80.9% (95% CI, 73.9%, 86.2%). The ENVISION trial also met its primary endpoint, showing a 79.6% (95% CI, 73.9%, 84.5%) CR rate at three months in patients treated with UGN-102.

"These data from the ENVISION trial provide compelling evidence that treatment with UGN-102 achieves a clinically meaningful complete response rate and also demonstrates remarkable durability in patients with LG-IR-NMIBC," said Sandip Prasad, MD, M.Phil., Director of Genitourinary Surgical Oncology at Morristown Medical Center/Atlantic Health System, NJ, and Principal Investigator of the ENVISION trial. "The long-term results, with 82.3% duration of response at 12 months, further strengthen UGN-102’s potential as a non-surgical, effective treatment for patients facing the recurrent and challenging nature of LG-IR-NMIBC."

According to Mark Schoenberg, M.D., Chief Medical Officer, UroGen, "The impressive duration of response data from the ENVISION trial further highlights UGN-102’s potential to transform the treatment landscape for patients with LG-IR-NMIBC. Many of these patients are elderly and face the burden of repeated surgeries under general anesthesia, so there is a critical need for innovative treatment options for this patient population. We believe that, if approved, UGN-102’s ability to achieve durable complete responses and potentially reduce recurrence rates while extending treatment-free intervals will represent a significant advance in managing LG-IR-NMIBC."

UroGen initiated the submission of a rolling New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for UGN-102 as a treatment for LG-IR-NMIBC in January 2024 and completed the NDA submission in August, ahead of schedule. The FDA accepted the NDA for UGN-102 with a PDUFA goal date of June 13, 2025.

The most common treatment-emergent adverse events (TEAEs) in the ENVISION trial were dysuria, hematuria, urinary tract infection, pollakiuria, fatigue, and urinary retention. The TEAEs were typically mild-to-moderate in severity and either resolved or were 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 enable longer exposure of bladder tissue to mitomycin, thereby enabling the treatment of tumors by non-surgical means. 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 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 23,000 newly diagnosed bladder cancer patients each year and an estimated 59,000 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.

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 chemoablative therapy in 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 January 15, 2025 Orna Therapeutics, Inc. ("Orna") and Shanghai Simnova Biotech Co., Ltd. ("Simnova") reported the expansion of their strategic collaboration to include BCMA (B-cell maturation antigen) as a designated biological target for RNA-based therapeutics development (Press release, Orna Therapeutics, JAN 15, 2025, View Source [SID1234649741]). This partnership leverages Orna’s groundbreaking circular RNA (oRNA) technology and Simnova’s expertise in cell therapy to deliver transformative treatments for patients worldwide.

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Under the agreement, Simnova will pursue the research and development and commercialization of in vivo panCar cell therapies targeting BCMA in greater China and Orna will retain all rights for development and commercialization in the rest of the world. Each party will have the right to receive an upfront payment within their respective licensed territories and is eligible for clinical development, regulatory, and commercialization milestones as well as royalties on any approved products derived from the collaboration.

In January 2023, Simnova and Orna announced a collaboration agreement granting Simnova exclusive rights to develop and commercialize Orna’s in vivo cell therapy products in the Greater China region. This includes Orna’s lead isCAR project targeting CD19, "ORN-101."

"We are excited to deepen our partnership with Simnova to bring an in vivo BCMA panCAR therapy to patients with multiple Myeloma," said Ansbert Gadicke, M.D., Chairman of Orna and Managing Partner of MPM BioImpact. "Orna’s panCAR approach holds the potential to introduce a novel class of in vivo CAR therapies that overcomes the limitations of current ex vivo cell therapies. The exciting pre-clinical and non-human primate data that Orna has generated continues to reinforce our commitment in this area. We look forward to advancing our programs towards the clinic."

Dr. Zhuoxiao CAO, CEO of Simnova, added, "Our shared commitment to advancing immunotherapies and oncology treatments opens new opportunities to address unmet medical needs through the development of BCMA-targeted therapeutics."

On January 15, 2025 Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC), a leading clinical-stage company specializing in immunotherapy for oncology, reported that Germany’s medical regulatory body, the Paul-Ehrlich-Institute (PEI), has approved the continuation of patient enrollment into Cohort 5 of the GOBLET study (Press release, Oncolytics Biotech, JAN 15, 2025, View Source [SID1234649740]). This cohort is evaluating pelareorep in combination with modified FOLFIRINOX (mFOLFIRINOX) with or without atezolizumab (Tecentriq) in newly diagnosed pancreatic ductal adenocarcinoma (PDAC) patients.

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Following a positive safety review by the independent Data Safety Monitoring Board (DSMB), which recommended continuation, the PEI’s approval allows Cohort 5 to progress to full enrollment. Early safety data will be presented at the upcoming 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium later this month, with initial efficacy results expected in the second half of the year.

"Pelareorep has the potential to meaningfully improve outcomes for patients with metastatic pancreatic cancer," said Thomas Heineman, M.D., Ph.D., Chief Medical Officer for Oncolytics Biotech. "Encouraging tumor response rates observed in an earlier cohort of the GOBLET study underscore pelareorep’s promise in this disease. GOBLET Cohort 5 extends our evaluation by testing pelareorep with a different chemotherapy regimen, mFOLFIRINOX, which broadens the range of pancreatic cancer patients who may benefit from this innovative therapy. Positive results from this cohort may ultimately enable pelareorep to benefit the large majority of metastatic pancreatic patients for whom improved treatment options are badly needed."

About GOBLET Cohort 5
The mFOLFIRINOX cohort of the Phase 1/2 GOBLET study is designed to evaluate newly diagnosed metastatic PDAC patients treated with pelareorep + mFOLFIRINOX with or without atezolizumab. A three-patient safety run-in was incorporated to evaluate the safety and tolerability of each treatment arm: pelareorep + mFOLFIRINOX + atezolizumab and pelareorep + mFOLFIRINOX. A total of fifteen evaluable patients will be randomized to each arm in Stage 1 of this Simon two-stage study. The co-primary endpoints are objective response rate and safety. If Stage 1 success criteria are met, one or both treatment arms may be expanded to Stage 2, in which 17 additional evaluable patients per arm will be enrolled. Blood and tumor samples will also be collected for translational evaluations.

About GOBLET
The GOBLET (Gastrointestinal tumOrs exploring the treatment comBinations with the oncolytic reovirus peLarEorep and anTi-PD-L1) study is a phase 1/2 multiple indication study in advanced or metastatic gastrointestinal tumors. The study is being conducted at 17 centers in Germany and is being managed by AIO-Studien-gGmbH. The co-primary endpoints of the study are objective response rate (ORR) and/or disease control rate and safety. Key secondary and exploratory endpoints include additional efficacy assessments and evaluation of potential biomarkers. The study comprises five treatment groups:

1.Pelareorep in combination with atezolizumab, gemcitabine, and nab-paclitaxel in 1st line advanced/metastatic PDAC patients;

2.Pelareorep in combination with atezolizumab in 1st line MSI (microsatellite instability)-high metastatic colorectal cancer patients;

3.Pelareorep in combination with atezolizumab and TAS-102 in 3rd line metastatic colorectal cancer patients;

4.Pelareorep in combination with atezolizumab in 2nd line or later advanced and unresectable anal cancer patients; and

5.Pelareorep in combination with mFOLFIRINOX with and without atezolizumab in newly diagnosed metastatic PDAC patients.

Any cohort meeting pre-specified efficacy criteria in Stage 1 may be advanced to Stage 2 and enroll additional patients.

About AIO
AIO-Studien-gGmbH (AIO) emerged from the study center of the medical oncology working group within the German Cancer Society (DKG). AIO operates with a non-profit purpose of promoting science and research with a focus on medical oncology. Since its foundation, AIO has become a successful sponsor and study management company and has established itself both nationally and internationally.