On January 28, 2025 Taiho Pharmaceutical Co., Ltd., Taiho Oncology, Inc., and Cullinan Therapeutics, Inc., reported that the REZILIENT1 trial, a Phase 1/2 clinical trial of zipalertinib (development code: CLN-081/TAS6417) monotherapy in patients with non-small cell lung cancer (NSCLC) harboring the epidermal growth factor receptor (EGFR) exon 20 insertion mutations who have received prior therapy, met its primary endpoint of overall response rate (Press release, Taiho, JAN 28, 2025, View Source [SID1234649911]). The safety profile was generally consistent with previous data presentations. These results are based on the Phase 2b part of this study.

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Full results from REZILIENT1 will be submitted for presentation at an upcoming international medical conference. Pending discussions with the U.S. Food and Drug Administration (FDA), the companies plan to submit for U.S. regulatory approval in the second half of 2025.

About the REZILIENT1 Trial
REZILIENT1 is a Phase 1/2 clinical trial (NCT04036682) to evaluate efficacy and safety of zipalertinib in patients with NSCLC harboring EGFR exon 20 insertion mutations who have received prior therapy. The topline results obtained at this time are based on the Phase 2b part of this study. Preliminary results of REZILIENT1 have been published in the Journal of Clinical Oncology.1

REZILIENT: Researching Zipalertinib In EGFR Non-Small Cell Lung Cancer Tumors

About Zipalertinib
Zipalertinib (development code: CLN-081/TAS6417) is an orally available small molecule designed to target activating mutations in EGFR. The molecule was selected because of its ability to inhibit EGFR variants with exon 20 insertion mutations, while sparing wild-type EGFR. Zipalertinib is designed as a next generation, irreversible EGFR inhibitor for the treatment of a genetically defined subset of patients with non-small cell lung cancer. Zipalertinib has received Breakthrough Therapy Designation from the FDA.

Zipalertinib is being developed by Taiho Oncology, Inc., its parent company, Taiho Pharmaceutical Co., Ltd., and in collaboration with Cullinan Therapeutics, Inc. in the U.S.

About the EGFR exon 20 insertion mutations
NSCLC is a common form of lung cancer and up to 4% of all cases have EGFR exon 20 insertions, which makes them the third most common EGFR mutation subtype.2 In the United States, approximately 16% of patients with NSCLC harbor EGFR mutations, with insertions at exon 20 accounting for up to 12% of these mutations.

On January 28, 2025 Sonnet BioTherapeutics Holdings, Inc. (the "Company" or "Sonnet") (NASDAQ: SONN), a clinical-stage company developing targeted immunotherapeutic drugs, reported that the European Patent Office (EPO) has granted Patent No. EP3583125 B1, entitled "Albumin Binding Domain Fusion Proteins," which covers Sonnet’s Fully Human Albumin Binding (FHAB) technology and includes therapeutic fusion proteins that utilize FHAB for tumor targeting and retention and provide extended pharmacokinetics (PK) (Press release, Sonnet BioTherapeutics, JAN 28, 2025, View Source [SID1234649908]). The EU patent carries a term effective until February 20, 2038. Additionally, the Company announced the release of a "What This Means" segment to discuss the EU patent and its global IP estate, which is now available here.

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"The granting of this EU patent represents another milestone that provides expanded global protection along with building our intellectual capital and differentiation from any existing or emerging competitive technologies that may leverage the beneficial characteristics of binding to human serum albumin," commented Pankaj Mohan, Ph.D., Founder and CEO of Sonnet. "Further, this European patent issuance expands the global IP protection for our product pipeline beyond previous patents issued in China, Japan, Russia and New Zealand, which we believe provides further validation for our FHAB platform."

Sonnet’s FHAB platform consists of a single, fully human construct of a FHAB antibody fragment that has high affinity to bind to human albumin. The platform provides an off-the-shelf lock and load opportunity to rapidly develop numerous therapeutic biologics.

John Cini, Ph.D., Co-Founder and CSO of Sonnet commented, "The FHAB platform technology provides each of Sonnet’s pipeline drug candidates with either a mono- or bi-functional mechanism of action, thus allowing for the potential of biological synergy between cytokines. Preclinical comparative in vivo studies with wild type cytokines have shown that FHAB-derived drug candidates have reproducibly extended pharmacokinetics, enhanced payload delivery to the tumor and improved efficacy."

On January 28, 2025 SELLAS Life Sciences Group, Inc. (NASDAQ: SLS) ("SELLAS" or the "Company"), a late-stage clinical biopharmaceutical company focused on the development of novel therapies for a broad range of cancer indications, reported that it has entered into a securities purchase agreement with a single healthcare-focused institutional investor for the purchase and sale of 19,685,040 shares of its common stock (or common stock equivalents in lieu thereof) and warrants to purchase up to an aggregate of 19,685,040 shares of common stock in a registered direct offering (the "Offering") at a combined purchase price of $1.27 per share and accompanying warrant, priced at-the-market under Nasdaq rules (Press release, Sellas Life Sciences, JAN 28, 2025, View Source [SID1234649907]). The warrants will have an exercise price of $1.20 per share, will be immediately exercisable upon issuance and will expire 5 years from issuance.

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The closing of the Offering is expected to occur on or about January 29, 2025, subject to the satisfaction of customary closing conditions. The gross proceeds from the Offering are expected to be approximately $25 million, before deducting placement agent fees and other estimated offering expenses. The Company intends to use the net proceeds from the Offering for working capital purposes and general corporate procedures, including the purchase of any pending or future acquisitions.

A.G.P./Alliance Global Partners is acting as lead placement agent for the Offering and Maxim Group LLC is acting as co-placement agent for the Offering.

The Offering is being made pursuant to an effective shelf registration statement on Form S-3 (File No. 333-278334) previously filed with the U.S. Securities and Exchange Commission (the "SEC"). A prospectus supplement describing the terms of the proposed Offering will be filed with the SEC and will be available on the SEC’s website located at View Source Electronic copies of the prospectus supplement may be obtained, when available, from A.G.P./Alliance Global Partners, 590 Madison Avenue, 28th Floor, New York, NY 10022, or by telephone at (212) 624-2060, 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 registration or qualification under the securities laws of any such state or other jurisdiction.

On January 28, 2025 Pfizer Inc. (NYSE: PFE) reported that it will present the latest results from its leading genitourinary (GU) portfolio at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary (ASCO GU) Cancers Symposium taking place February 13-15 in San Francisco, California (Press release, Seagen, JAN 28, 2025, View Source [SID1234649906]). Data from more than 20 company-sponsored, investigator-sponsored, and collaborative research abstracts, including five oral presentations, highlight advancements in developing new standards of care within prostate and bladder cancer across the company’s core scientific modalities, including small molecules and antibody-drug conjugates.

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"Our long-standing commitment to the genitourinary cancer community has been foundational in our mission to transform the treatment landscapes for patients with bladder and prostate cancers," said Karin Tollefson, Chief Oncology Medical Officer, Pfizer. "Our strong presence at this year’s ASCO (Free ASCO Whitepaper) GU highlights the longer-term impacts of our approved leading medicines for patients in their respective indications. We are also looking forward to sharing updates from our rapidly growing pipeline of novel targets and combination approaches, which have the potential to help address the diverse needs of patients across various stages of disease."

Pfizer’s GU portfolio includes seven approved medicines across bladder, prostate, and kidney cancers, as well as a growing late-stage pipeline of scientific modalities and combination approaches. Key Pfizer presentations at ASCO (Free ASCO Whitepaper) GU include the detailed overall survival (OS) results from the Phase 3 TALAPRO-2 trial with TALZENNA (talazoparib) plus XTANDI (enzalutamide) in patients with metastatic castration-resistant prostate cancer (mCRPC), which will be featured in ASCO (Free ASCO Whitepaper) GU’s official Press Program. In addition, updated analysis from the Phase 3 global EV-302 study of PADCEV (enfortumab vedotin-ejfv) in combination with pembrolizumab in locally advanced or metastatic urothelial cancer (la/mUC) will be presented, highlighting the long-term efficacy benefits of the combination.

From the pipeline, the first randomized progression-free survival (PFS) data from the ongoing Phase 1 dose-escalation study for mevrometostat plus XTANDI reinforce the potential of this investigational combination for patients with mCRPC. Additional pipeline presentations include updated data and real-world evidence for different types of bladder cancer, supporting the development of two potential transformative treatments, disitamab vedotin, an investigational antibody-drug conjugate (ADC), and sasanlimab, an investigational subcutaneous PD-1 blocker.

Key ASCO (Free ASCO Whitepaper) GU Presentations

Prostate Cancer

TALZENNA plus XTANDI:Oral and poster presentations from the pivotal Phase 3 TALAPRO-2 trial of TALZENNA in combination with XTANDI will provide detailed results on the statistically significant and clinically meaningful improvement in OS in all-comers (cohort 1) as well as in those patients with homologous recombination repair (HRR) gene-mutated mCRPC (cohort 2), compared to XTANDI alone. TALZENNA in combination with XTANDI has been approved for use in over 35 countries globally for patients with certain types of mCRPC*. The OS results will be shared with global health authorities to potentially update the TALZENNA label.
XTANDI: Six abstracts continue to underscore the benefit of XTANDI across its approved indications, including two posters highlighting follow-up analysis from the EMBARK trial of XTANDI in combination with leuprolide in patients with non-metastatic castration-sensitive prostate cancer with biochemical recurrence at high-risk for metastasis.
Mevrometostat: The first randomized PFS results from the ongoing Phase 1 dose-expansion study examine the potential of mevrometostat (PF-06821497), an investigational selective inhibitor of enhancer of zeste homolog 2 (EZH2), in combination with XTANDI in patients with mCRPC, compared to XTANDI alone. Pfizer initiated two pivotal Phase 3 trials for mevrometostat plus XTANDI in 2024 and expects to start a Phase 3 study of mevrometostat plus XTANDI in first-line mCSPC during the first half of 2025.
Bladder Cancer

PADCEV: Long-term follow-up data from the groundbreaking Phase 3 EV-302 study of PADCEV in combination with pembrolizumab, including OS and safety data, continue to demonstrate consistent efficacy versus chemotherapy in a broad population, reinforcing the combination as standard of care in first-line treatment of la/muC.
Disitamab vedotin: Updated efficacy and safety data from an ongoing Phase 2 study (sponsored by Remegen) evaluating the HER2-targeting ADC disitamab vedotin plus toripalimab show encouraging results as a perioperative regimen in HER2-expressing muscle-invasive bladder cancer (MIBC). These data add to the growing body of evidence supporting the continued development of disitamab vedotin across stages of bladder cancer.
Sasanlimab: Three real-world evidence poster presentations highlight the need for advanced treatment options for patients with non-muscle invasive bladder cancer (NMIBC), including presentations on Bacillus Calmette-Guérin (BCG) treatment patterns, impact of BCG shortages, and outcomes and treatment patterns in patients with high-risk NMIBC. Pfizer recently reported positive topline results for sasanlimab in combination with BCG as induction therapy with or without maintenance in patients with BCG- naïve, high-risk NMIBC. Detailed results from the Phase 3 CREST trial will be presented at an upcoming congress.
Additional information on key Pfizer-sponsored abstracts at ASCO (Free ASCO Whitepaper) GU 2025, including date and time of presentation, follow in the chart below. A complete list of Pfizer-sponsored accepted abstracts is available here.

*TALZENNA in combination with XTANDI was approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with HRR gene-mutated mCRPC in June 2023.

Prostate Cancer

Final overall survival (OS) with talazoparib (TALA) + enzalutamide (ENZA) as first-line treatment in unselected patients with metastatic castration-resistant prostate cancer (mCRPC) in the Phase 3 TALAPRO-2 trial (Abstract #LBA18)

Agarwal, N

Oral Abstract Session

Thursday, February 13, 11:42 AM – 11:52 AM EST

Presentation Time: 8:42 AM – 8:52 AM PST

Final overall survival (OS) with talazoparib (TALA) + enzalutamide (ENZA) as first-line (1L) treatment in patients (pts) with homologous recombination repair (HRR)-deficient metastatic castration-resistant prostate cancer (mCRPC) in the Phase 3 TALAPRO-2 trial (Abstract #LBA141)

Fizazi, K

Poster Session

Thursday, February 13, 2:25 PM – 3:45 PM EST

Presentation Time: 11:25 AM – 12:45 PM PST

Mevrometostat (PF-06821497), an enhancer of zeste homolog 2 (EZH2) inhibitor, in combination with enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC): A randomized dose-expansion study (Abstract #LBA138)

Schweizer, MT

Rapid Oral Abstract Session

Thursday, February 13, 8:25 PM – 8:30 PM EST

Presentation Time: 5:25 PM – 5:30 PM PST

Bladder Cancer

EV-302: Updated analysis from the phase 3 global study of enfortumab vedotin in combination with pembrolizumab (EV+P) vs chemotherapy (chemo) in previously untreated locally advanced or metastatic urothelial carcinoma (la/mUC) (Abstract #664)

Powles, TB

Rapid Oral Abstract Session

Friday, February 14, 7:10 PM – 7:15 PM EST

Presentation Time: 4:10 PM – 4:15 PM PST

Neoadjuvant treatment with disitamab vedotin plus perioperative toripalimab in patients with muscle-invasive bladder cancer (MIBC) with HER2 expression: Updated efficacy and safety results from the phase II RC48-C017 trial (Abstract #665)

Sheng, X

Oral Abstract Session

Friday, February 14, 11:57 AM – 12:07 PM EST

Presentation Time: 8:57 AM – 9:07 AM PST

On January 28, 2025 Leap Therapeutics, Inc. (Nasdaq:LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, reported positive initial data from Part B of the DeFianCe study evaluating sirexatamab (DKN-01) in combination with bevacizumab and chemotherapy as a second-line treatment for patients with advanced colorectal cancer (CRC), and initial data from Part C of the DisTinGuish study evaluating sirexatamab in combination with tislelizumab and chemotherapy in first-line patients with advanced gastroesophageal junction (GEJ) and gastric cancer (Press release, Leap Therapeutics, JAN 28, 2025, View Source [SID1234649905]).

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Key Findings from Part B of the DeFianCe study:

"Data from Part B of the DeFianCe study closely mirror the findings from Part A, and together they demonstrate the potential of sirexatamab to provide a compelling treatment option for second-line CRC patients who do not benefit from current standard of care," said Cynthia Sirard, M.D., Chief Medical Officer of Leap. "Along with consistently achieving higher response rates than the control arm, the data also point to a favorable safety profile. While not yet fully mature, we are encouraged by the progression-free survival data thus far across key subgroups in the study. We look forward to reporting additional data from Part B as it matures over the coming months and beginning our planning for Phase 3 registrational studies."

"The patient population in second-line CRC is heterogeneous, and there is a true unmet need for new treatment options that are safe and effective. The latest findings from DeFianCe Part B are highly encouraging, as sirexatamab combination therapy is outperforming bevacizumab and chemotherapy alone in ORR in the intent-to-treat analysis and across key subgroups of interest," said Zev Wainberg, M.D., Professor of Medicine and Co-Director of the GI Oncology Program at UCLA. "Initial results also show increased response rates in patients with high DKK1 levels, directly correlating with sirexatamab’s novel mechanism of action. These data support moving forward into Phase 3 registrational studies to further explore a unique treatment option for patients in need."

The DeFianCe study (NCT05480306) is a Phase 2, open-label, global study of sirexatamab in combination with bevacizumab and chemotherapy in patients with advanced microsatellite stable (MSS) CRC who have received one prior systemic therapy for advanced disease. Part B of the study is a 188 patient randomized controlled trial, with the primary objective being progression-free survival (PFS) in patients with left-sided cancers and in all patients. Key secondary and exploratory objectives include objective response rate (ORR), duration of response, and overall survival across tumor, treatment, and biomarker subgroups.

· Across the intent-to-treat (ITT) population with second-line MSS CRC (n=188):
o Patients treated with sirexatamab plus bevacizumab and chemotherapy (Experimental Arm, n=94) had ORR of 35% and disease control rate (DCR) of 86%, compared to an ORR of 23% and DCR of 84% in patients treated with bevacizumab and chemotherapy alone (Control Arm, n=94)

· Across the population with left-sided primary tumors (n=144):
o Patients treated in the Experimental Arm (n=71) had an ORR of 38%, compared to an ORR of 25% in the Control Arm (n=73)

· Plasma DKK1 highly correlated with clinical activity:
o Patients in the Experimental Arm with DKK1 levels above the median (n=49) had an ORR of 39%, compared to 22% ORR in the Control Arm (n=36)
o Patients in the upper-quartile of DKK1 levels in the Experimental Arm (n=25) had an ORR of 48%, compared to 11% ORR in the Control arm (n=18)

· Key patient subgroups demonstrated higher ORR in the Experimental Arm:
o No prior anti-VEGF therapy: Patients in the Experimental Arm (n=49) had an ORR of 51%, compared to 29% ORR in the Control arm (n=45)
o Prior anti-EGFR therapy: Patients in the Experimental Arm (n=28) had an ORR of 54%, compared to 27% ORR in the Control arm (n=22)
o RAS wildtype (RAS-wt) tumors: Patients in the Experimental Arm (n=35) had an ORR of 43%, compared to 32% ORR in the Control Arm (n=25)

· With only 3 months follow-up on the final patients enrolled and mean duration on study of approximately 6 months, PFS is not yet mature. Eighty-two patients are still on study, 46 in the Experimental Arm and 36 in the Control Arm. Early separation in the Kaplan-Meier PFS curves is being seen in many of the key patient subgroups, including DKK1 biomarker, anti-VEGF-naïve, anti-EGFR-experienced, and RAS-wt patients. Leap expects to report additional data as it matures in 2025.

· Sirexatamab plus bevacizumab and chemotherapy was well-tolerated, without additive toxicity to the standard of care.

The strong signal in CRC from the DeFianCe study supports Leap moving forward to plan a registrational Phase 3 clinical trial to evaluate sirexatamab plus bevacizumab and chemotherapy in second-line MSS CRC patients with high unmet need, subject to regulatory discussions. Potential Phase 3 patient populations include: DKK1 biomarker-selected, anti-VEGF naïve, anti-EGFR experienced, or RAS-wt patients. While the data matures, Leap intends to conduct global commercial and regulatory strategic analysis to select the optimal population.

Key Findings from Part C of the DisTinGuish study:

Leap also reported data from Part C of the DisTinGuish study evaluating sirexatamab in combination with tislelizumab, BeiGene’s anti-PD-1 antibody, and chemotherapy in first-line patients with advanced GEJ and gastric cancer. While demonstrating activity in biomarker populations, the study did not generate a clear positive signal and will be negative on the primary PFS endpoints when the study completes, resulting in the decision not to move forward with Phase 3 studies in gastric cancer.

"Sirexatamab plus tislelizumab and chemotherapy demonstrated improved confirmed response rates compared to the control arm in the ITT, DKK1-high, and PD-L1 negative patients by Blinded Independent Central Review (BICR). However, gastric cancer is a difficult tumor to assess radiologically, and unfortunately, there was a high level of discordance between investigator assessment (IA) and BICR," said Dr. Sirard. "Therefore, we have decided to focus our internal effort and resources on advancing sirexatamab in CRC and will explore strategic partnership opportunities to advance sirexatamab plus anti-PD-1 antibodies in gastric cancer and other indications where there is high DKK1 expression."

Part C of the DisTinGuish study (NCT0436380) is a Phase 2, randomized, open-label, multicenter study of sirexatamab in combination with tislelizumab and chemotherapy in first-line patients with advanced GEJ and gastric cancer. Part C enrolled 170 first-line, HER2-negative patients. Patients were randomized 1:1 to evaluate sirexatamab in combination with tislelizumab and chemotherapy, compared to tislelizumab and chemotherapy alone. The primary objective is PFS by IA in all patients and in DKK1 TPS > 20 (DKK1-high) patients. Secondary objectives include ORR, duration of response, and overall survival as measured by BICR and IA in all patients and in DKK1-high patients.

· Across the ITT population (n=170), patients treated with sirexatamab plus tislelizumab and chemotherapy (Experimental Arm, n=85) had a confirmed ORR of 52% by both IA and BICR, while patients treated with tislelizumab and chemotherapy alone (Control Arm, n=85) had a confirmed ORR of 56% by IA and 42% by BICR.

· Based on BICR:
o Patients in the Experimental Arm with DKK1-high tumors (n=22) had a confirmed ORR of 59%, compared to 36% in the Control Arm (n=22)
o Patients in the Experimental Arm with PD-L1-negative tumors (n=18) had a confirmed ORR of 44%, compared to 32% in the Control Arm (n=19)

· In the ITT population, preliminary median PFS in the Experimental Arm was 9.72 months by BICR and 7.66 months by IA compared to 11.99 months by BICR and 10.41 months by IA in the Control Arm. The median PFS for tislelizumab plus chemotherapy in the Phase 3 Rationale-305 study was 6.9 months (95% CI: 5.7, 7.2).

· In the DKK1-high population, preliminary median PFS in the Experimental Arm was 7.72 months by BICR and 7.43 months by IA compared to 7.79 months by BICR and 11.14 months by IA in the Control Arm. The hazard ratio for PFS by BICR was 0.68, representing a trend in favor of the Experimental Arm in the overall time to event analysis.

· Sirexatamab plus tislelizumab and chemotherapy was well tolerated, without additive toxicity to the standard of care.

Conference Call:

Leap’s management team will host a conference call today, January 28, 2025 at 8:00 a.m. Eastern Time to further discuss the data. The conference call will be broadcast live in listen-only mode and can be accessed via the webcast URL: View Source A replay of the event will be available for a limited time on the Investors page of the Company’s website at View Source