1stOncology™: Cancer Intelligence Service – Page 1431 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

Innovent Receives NMPA Breakthrough Therapy Designation for IBI343 (Anti-CLDN18.2 ADC) as Monotherapy for Advanced Pancreatic Cancer

On January 15, 2025 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, cardiovascular and metabolic, autoimmune, ophthalmology and other major diseases, reported that the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) has granted Breakthrough Therapy Designation (BTD) for IBI343, a potentially best-in-class TOPO1i anti-CLDN18.2 ADC, as monotherapy for the treatment of CLDN18.2-positive advanced pancreatic ductal adenocarcinoma (PDAC) patients who have progressed after at least one line of prior systematic treatment (Press release, Innovent Biologics, JAN 15, 2025, View Source [SID1234649747]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

Schedule Your 30 min Free Demo!

The BTD for IBI343 was granted based on data from an ongoing Phase 1 study conducted in China, Australia and the U.S. (NCT05458219), which demonstrated favorable safety and tolerability, as well as promising antitumor activity of IBI343 monotherapy in advanced PDAC patients. Data from the study’s dose-expansion cohort were presented orally at the 2024 ESMO (Free ESMO Whitepaper) Asia Congress:

A total of 43 patients with CLDN18.2-positive advanced PDAC (≥60% tumor cells with membranous staining intensity ≥1+ by IHC) received IBI343 6 mg/kg Q3W monotherapy. All participants had previously received at least one line of prior therapy, and 60.5% had received two or more lines of anticancer treatment.
The confirmed overall objective response rate (ORR) was 23.3%, and progression-free survival (PFS) events occurred in 26 patients, with a median progression-free survival (mPFS) of 5.3 months (4.1-7.4) as of the data cutoff date. (link)
Previously, in May 2024, the CDE has granted IBI343 its first BTD for monotherapy in the treatment of CLDN18.2-positive advanced gastric/gastro-esophageal junction adenocarcinoma (GC) patients who have progressed after at least two lines of prior systematic treatments. In addition, in June 2024, IBI343 was granted Fast Track Designation by the U.S. Food and Drug Administration (FDA) for the treatment of advanced, unresectable or metastatic PDAC that has relapsed and/or is refractory to one prior line of therapy. The first patient in the U.S. Phase 1 study of IBI343 was successfully dosed in December 2024.

Dr. Hui Zhou, Senior Vice President of Innovent, said, "Pancreatic cancer is an aggressive and difficult-to-diagnose malignancy. At present, treatment for advanced pancreatic cancer relies primarily on systemic chemotherapy, with particularly limited options for second-line treatment. This results in poor patient outcomes and underscores an urgent unmet clinical need. As the world’s first CLDN18.2 ADC to receive BTD in this difficult-to-treat cancer, IBI343 monotherapy has shown encouraging efficacy and tolerable safety in late-line treatment of patients with advanced pancreatic cancer. Subject to PoC data readout, we plan to initiate pivotal MRCT studies to further confirm its efficacy and safety in this indication. Additionally, we will also explore the potential of IBI343 in combination therapy for pancreatic cancer and other solid tumors, including gastric cancer."

NMPA Breakthrough Therapy Designation is intended to facilitate and expedite the development and review of investigational drugs for serious diseases or conditions when preliminary clinical evidence indicates substantial improvement over current therapies. BTD qualifies a drug candidate for accelerated review by the CDE and provides the sponsor with timely advice and communication to expedite the approval process, helping to address the unmet clinical needs of patients more swiftly.

About Pancreatic Ductal Adenocarcinoma

Pancreatic cancer is one of the most aggressive malignances of the digestive system, with a 5-year survival rate of about 10%[i]. Despite rising incidence rates in recent years, early detection remains low, seriously endangering human life and health. Current treatment for advanced pancreatic cancer is primarily based on systemic chemotherapy, with first-line treatment options typically including fluorouracil (5-FU) or gemcitabine-based chemotherapy. However, second-line treatment options are limited, offering a chemotherapy response rate of only 6-16%, a median progression free survival of 2 to 5 months, and a median overall survival of approximately 6 to 9 months[ii]. These statistics highlight the urgent need for new therapeutic approaches.

Claudin, a member of the tight junction molecule family, is a key structural and functional component of epithelial tight junctions. Among them, CLDN18.2 is normally confined to the gastric mucosa. The development of malignancy leads to disruption of tight junctions and exposure of CLDN18.2 epitopes on the membrane of tumor cells[iii]. CLDN18.2 is present in 50% to 70% of pancreatic cancer cases, making it a highly targeted biomarker for therapeutic development[iv].

About IBI343 (CLDN18.2 ADC)

IBI343 is an antibody-drug conjugate composed of an anti-CLDN18.2 antibody, and a cytotoxic drug exatecan. Binding of IBI343 to CLDN18.2-expressing tumor cells results in CLDN18.2-dependent internalization of IBI343. Degradation of the cleavable linker will release the drug that causes DNA damage, leading to apoptosis of the tumor cells. The freed drug can also diffuse across the plasma membrane to reach and kill the neighboring tumor cells, resulting in a strong "bystander killing effect" of IBI343. As an innovative TOPO1i ADC, IBI343 has demonstrated tolerable safety and encouraging efficacy signals in Phase 1 clinical studies. The therapeutic potential of IBI343 is currently being explored in tumor types such as gastric and pancreatic cancers, including a Phase 3 trial (NCT06238843) for GC and a multi-regional Phase 1 trial (NCT05458219) for PDAC ongoing.

IBI343 was granted breakthrough therapy designation (BTD) by China’s National Medical Products Administration (NMPA) for two indications, as monotherapy in patients with CLDN18.2–positive GC who progressed after two prior lines of systemic treatment, and in patients with CLDN18.2-positive PDAC who have progressed after at least one line of prior systematic treatment. IBI343 also received Fast Track Designation by the U.S. Food and Drug Administration (FDA) for the treatment of advanced unresectable or metastatic PDAC that has relapsed and/or is refractory to one prior line of therapy.

Phio Pharmaceuticals Announces $2.5 Million Registered Direct Offering Priced At-the-Market Under Nasdaq Rules

On January 15, 2025 Phio Pharmaceuticals Corp. (NASDAQ: PHIO), a clinical-stage biotechnology company that develops therapeutics using its INTASYL siRNA gene silencing technology to make the body’s immune cells more effective in killing cancer cells, reported that it has entered into definitive agreements for the purchase and sale of an aggregate of 833,335 shares of its common stock at a purchase price of $3.00 per share in a registered direct offering priced at-the-market under Nasdaq rules (Press release, Phio Pharmaceuticals, JAN 15, 2025, View Source [SID1234649745]). In addition, in a concurrent private placement, the Company will issue short-term unregistered warrants to purchase up to an aggregate of 1,666,670 shares of common stock. The short-term warrants will have an exercise price of $3.00 per share, will be exercisable upon issuance and expire twenty-four months following the date of issuance. The closing of the offering is expected to occur on or about January 15, 2025, subject to the satisfaction of customary closing conditions.

H.C. Wainwright & Co. is acting as the exclusive placement agent for the offering.

The aggregate gross proceeds to the Company from the offering are expected to be $2.5 million, before deducting the placement agent fees and other offering expenses payable by the Company. The Company currently intends to use the net proceeds from the offering for working capital and other general corporate purposes.

The shares of common stock (but not the short-term warrants issued in the private placement or the shares of common stock underlying such short-term warrants) are being offered by the Company pursuant to a "shelf" registration statement on Form S-3 (File No. 333-279557) filed with the Securities and Exchange Commission ("SEC") on May 20, 2024 and became effective on July 1, 2024. The registered direct offering of the shares of common stock is being made only by means of a prospectus, including a prospectus supplement, forming a part of the effective registration statement. The prospectus supplement and the accompanying prospectus relating to the shares of common stock being offered in the registered direct offering will be filed with the SEC and be available at the SEC’s website at www.sec.gov. Electronic copies of the prospectus supplement and the accompanying prospectus relating to the registered direct offering may also be obtained, when available, by contacting H.C. Wainwright & Co., LLC at 430 Park Avenue, 3rd Floor, New York, NY 10022, by telephone at (212) 856-5711 or e-mail at [email protected].

The short-term warrants described above are being issued in a concurrent private placement under Section 4(a)(2) of the Securities Act of 1933, as amended (the "Securities Act"), and Regulation D promulgated thereunder and, along with the shares of common stock underlying the short-term warrants, have not been registered under the Securities Act, or applicable state securities laws. Accordingly, the short-term warrants and underlying shares of common stock may not be offered or sold in the United States except pursuant to an effective registration statement or an applicable exemption from the registration requirements of the Securities Act and such applicable state securities laws.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy any of the securities described herein, nor shall there be any sale of these securities in any state or 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 jurisdiction.

XENOTHERA reaches important milestones in its oncology and onco-hematology clinical trials.

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.

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.

XENOTHERA successfully secures €4 Million non-dilutive financing from the France 2030 Public Investment Plan for its LIS22 treatment for peripheral T-Cell lymphoma.

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%.

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.

ENVISION Trial Results Published in the February Issue of The Journal of Urology Highlight UGN-102 Achievement of 82.3% Duration of Response at 12 Months Paving the Way for the Potential First FDA-Approved Treatment for LG-IR-NMIBC in June 2025

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]).

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).