On January 22, 2025 Tyra Biosciences, Inc. (Nasdaq: TYRA), a clinical-stage biotechnology company focused on developing next-generation precision medicines that target large opportunities in Fibroblast Growth Factor Receptor (FGFR) biology, reported that two abstracts were accepted for presentation at the 2025 ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium (ASCO GI), taking place January 23-25, 2025, in San Francisco, CA (Press release, Tyra Biosciences, JAN 22, 2025, View Source [SID1234649834]).

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Details of the poster presentations are below:

Title: "A multicenter, open-label, first-in-human study of TYRA-200 in advanced intrahepatic cholangiocarcinoma and other solid tumors with activating FGFR2 gene alterations (SURF201)"
Abstract: TPS646
Presenting Author: Robin Kate Kelley, MD, University of California San Francisco
Session: Trials in Progress Poster Session B: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract
Date/Time: January 24, 2025, 11:30 AM – 1:00 PM PST, Level 1, West Hall

Title: "TYRA-430: First reversible FGFR4/3 inhibitor designed to overcome current challenges in FGF19-driven hepatocellular carcinoma treatment"
Abstract: 583
Presenting Author: Ronald Swanson, Ph.D., Tyra Biosciences
Session: Poster Session B: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract
Date/Time: January 24, 2025, 11:30 AM – 1:00 PM PST, Level 1, West Hall

The abstracts related to these posters and additional information can be found on the ASCO (Free ASCO Whitepaper) GI website.

About TYRA-200

TYRA-200 is an oral, investigational, FGFR1/2/3 inhibitor with potency against activating FGFR2 gene alterations and resistance mutations. The Phase 1 clinical study of TYRA-200, SURF201 (Study in PrevioUsly treated and Resistant FGFR2+ Cholangiocarcinoma and Other Advanced Solid Tumors) (NCT06160752), is a multi-center, open label study designed to evaluate the maximum tolerated dose (MTD) and the recommended Phase 2 dose of TYRA-200, as well as to evaluate the preliminary antitumor activity of TYRA-200. SURF201 is currently enrolling and dosing adults with advanced/metastatic intrahepatic cholangiocarcinoma and other advanced solid tumors with activating alterations in FGFR2.

About TYRA-430

TYRA-430 is an oral, investigational FGFR4/3-biased inhibitor for FGF19+/FGFR4-driven cancers. The US Food and Drug Administration has cleared Tyra’s Investigational New Drug application to proceed with a Phase 1 clinical study of TYRA-430. The Phase 1 study will be a multicenter, open-label, first-in-human study of TYRA-430 in advanced hepatocellular carcinoma (HCC) and other solid tumors with activating FGF/FGFR pathway aberrations (SURF431).

On January 22, 2025 ImaginAb, Inc., reported that it has entered into an agreement to sell a pipeline of next-generation therapeutic candidates, proprietary novel biologics technology platform, and a protein engineering and discovery research facility to Telix Pharmaceuticals Limited (ASX: TLX; Nasdaq: TXL) (Press release, ImaginAb, JAN 22, 2025, View Source [SID1234649833]).

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Following the closing of this transaction, ImaginAb Inc., will focus on developing its lead imaging candidate, CD8 ImmunoPET, which is currently in Phase 2 clinical trials and has been licensed by numerous pharmaceutical and biotech companies for use in imaging within immunotherapy clinical trials, primarily in oncology. In addition, ImaginAb will continue to partner in advancing the pivotal prostate cancer imaging agent, which is currently being evaluated in Phase 2 clinical trials and as a surgical resection tool.

Dr. Anna Wu, Founder of ImaginAb, commented, "We are very pleased that Telix recognizes the potential of our novel biological technology platform including enabling Telix to explore new disease areas with state-of-the-art radiotherapeutic technology. These radiopharmaceutical agents represent the culmination of significant effort and resources by our scientific team. I extend my congratulations to everyone at ImaginAb for reaching this significant milestone. This transaction further validates our novel minibody platform."

Dr. Wu continued, "With the sale of our radiopharmaceutical platform, ImaginAb will continue the development of its CD8 platform. We are encouraged that numerous pharmaceutical and biotech companies have incorporated our technology in their immuno-oncology clinical trials."

Jefferies LLC and Stifel, Nicolaus & Company, Incorporated served as financial advisors to ImaginAb on the transaction.

On January 22, 2025 Akeso, Inc. (9926.HK) ("Akeso" or the "Company") reported that the prestigious medical journal Nature Medicine published the results of the company’s independently developed PD-1/CTLA-4 bispecific antibody cadonilimab in combination with oxaliplatin and capecitabine for the first-line treatment of unresectable locally advanced or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma in a Phase III clinical study (COMPASSION-15/AK104-302) (Press release, Akeso Biopharma, JAN 22, 2025, View Source [SID1234649832]). The results of the COMPASSION-15 study were previously orally presented at the 2024 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting.

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This recognition represents an additional validation of cadonilimab’s clinical value in addressing critical unmet need. Previously, clinical research findings on cadonilimab in the treatment of various malignancies have been published in internationally renowned journals such as The Lancet, The Lancet Oncology, Nature Medicine, Drugs, and Clinical Cancer Research.

The Phase III clinical data in the Nature Medicine publication indicates that, regardless of PD-L1 expression, cadonilimab combined with chemotherapy regimen significantly improves overall survival benefits for the entire population of advanced gastric cancer patients and reduces the risk of disease-related death (OS HR 0.62). Even for the PD-L1 low-expressing and negative group, the cadonilimab regimen demonstrated a meaningful survival benefit for patients (OS HR 0.70), effectively addressing the current limitations of PD-1 monoclonal antibody first-line treatment for PD-L1 low-expression and negative gastric cancer.

In September 2024, the cadonilimab regimen for the first-line treatment of advanced gastric cancer was approved and is now widely used in clinical practice, offering a comprehensive and efficacious immunotherapy option for patients. A Phase III clinical trial of cadonilimab combined with a VEGFR-2 monoclonal antibody for PD-1/L1 inhibitor-pretreated advanced gastric adenocarcinoma and gastroesophageal junction adenocarcinoma patients is currently advancing on scheduling. Akeso’s comprehensive clinical strategy for both first-line and subsequent-line treatments in various cancer types will further expand cadonilimab’s indications, providing a novel and effective solution for these patients. Cadonilimab’s ability to target both PD-1 and CTLA-4, two key immune checkpoints, demonstrates its synergistic anti-tumor mechanisms, further demonstrating Akeso’s leadership in the global bispecific antibody field for cancer immunotherapy.

Currently, cadonilimab is being investigated in over 23 clinical studies across 16 indications, targeting tumor types such as gastric cancer, lung cancer, liver cancer, cervical cancer, and pancreatic cancer. In addition to the already approved indications for recurrent/metastatic cervical cancer and first-line gastric cancer, as well as the first-line cervical cancer indication currently under review, cadonilimab is also undergoing five Phase III clinical trials for liver cancer, non-small cell lung cancer, and gastric cancer. Research across multiple indications, including cervical cancer, gastric cancer, and non-small cell lung cancer, has demonstrated that cadonilimab exhibits breakthrough efficacy across "broad population", demonstrating clinically meaningful positive outcomes for PD-L1 high-expressing, low-expressing, and even PD-L1-negative patient populations. Clinical benefit across multiple cancer types and tumor PD-L1 expression status shows that cadonilimab not only advances current cancer immunotherapies, but also significantly broadens their patient coverage. Cadonilimab holds the potential to become a cornerstone drug in the next generation of cancer immunotherapy and is expected to be widely used in combination with antibody-drug conjugates (ADCs) and other high-potential targets.

On January 22, 2025 Agenus Inc. (Nasdaq: AGEN ), a leader in immuno-oncology, reported new data on botensilimab (BOT) and balstilimab (BAL) at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium (ASCO GI) in San Francisco (Press release, Agenus, JAN 22, 2025, View Source [SID1234649831]). Data from five presentations underscore the transformative potential of BOT/BAL across multiple lines of therapy in colorectal cancer, including neoadjuvant, first-line, and refractory settings. Data presented also highlight BOT/BAL’s potential in treating microsatellite stable (MSS) CRC tumors, which account for 85-95%1 of patients living with CRC that historically have been unresponsive to immuno-oncology (I/O) therapies. To date, BOT/BAL has been evaluated in approximately 1,100 patients across more than 60 centers worldwide.

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"Data presented at ASCO (Free ASCO Whitepaper) GI highlight botensilimab and balstilimab’s potential to redefine colorectal cancer treatment, delivering remarkable outcomes in neoadjuvant MSS CRC," said Dr. Steven O’Day, Chief Medical Officer of Agenus . "These findings set the stage for pivotal studies intended to create a new standard of care for colon and rectal cancer patients by reducing reliance on chemotherapy, radiation, and surgery, while improving survival."

Key Data Highlights

Neoadjuvant CRC: A Potential Path to Chemo-Free Treatment

Data presented from two independent studies, UNICORN and NEST, collectively include more than 80 patients treated with BOT/BAL:

UNICORN: Phase 2 Trial of Pre-Operative BOT/BAL Combination Treatment in Resectable Colon Cancer (Abstract 158):
This multicenter Phase 2 study enrolled 56 patients across 10 centers in Italy and France.
Pathological complete responses (pCR) and pathological major responses (pMR) were observed in both the pMMR/MSS and dMMR/MSI-H patient populations.
BOT/BAL achieved a 93% pCR rate and 100% pMR in dMMR/MSI-H tumors and 29% pCR rate and 36% pMR rate in pMMR/MSS tumors, highlighting the opportunity for a non-operative, organ sparing, approach in this disease setting.
Serious adverse events (AEs) occurred in 9 pts (16%) and were treatment-related in 3 pts (5%). Only 1 of 56 surgeries were delayed due to an AE.
NEST: Phase 2 Trial of Neoadjuvant Combination Treatment of BOT/BAL in Patients with Resectable Colon Cancer (Abstract 207):
This trial has currently enrolled 24 patients.
After median follow-up of 18 months (NEST-1 arm) and 9 months (NEST-2 arm), all patients (100%) remained ctDNA negative and no clinical recurrences were observed. The pMR improved in NEST-2 to 47% (7/15) in MSS tumors when the median time to surgery was extended.
The combination was well tolerated with no grade 4 events and no unresolved immune-mediated adverse events (imAEs). No delays in surgery occurred due to imAEs.
Dr. Filippo Pietrantonio, Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori Milan comments on the UNICORN study stating, " These results further validate the transformative potential of botensilimab and balstilimab in colorectal cancer. The remarkable pathological response rates observed in both pMMR and dMMR tumors highlight the unique strength of this combination in addressing a critical unmet need and pave the way for non-operative management strategies."

First-Line and FOLFOX Rechallenged MSS CRC: Powerful Combination with Standard Therapies

Phase 1/2 Trial of BOT/BAL With FOLFOX-Bevacizumab in MSS mCRC (Abstract 180):
Preliminary findings showed activity of combination independent of liver metastases.
In the initial 14 patients, 12 which were previously treated with FOLFOX, a 71% overall response rate (ORR) was achieved. In the 9/14 patients with liver metastases, a 67% ORR was achieved.
The combination was well-tolerated with limited severe imAEs, supporting the opportunity for higher doses of BOT.
Refractory MSS CRC: Consistent Results Across Phase 1 and 2 Studies

Global Randomized Phase 2 Study of BOT/BAL in MSS mCRC NLM (Abstract 23):
This is a global Phase 2 trial (NCT05608044) of BOT/BAL versus standard-of-care treatments of regorafenib or trifluridine/tipiracil in patients with refractory metastatic colorectal cancer that had spread to either peritoneum, lymph nodes, lungs, bone or brain. 234 patients were enrolled across 40 centers worldwide.
These results reinforce the activity and safety seen in the Phase 1 study and confirm the contribution of BAL to BOT.
BOT75/BAL achieved a 19% ORR and 55% disease control rate (DCR) in this refractory population. Standard of care had no responses.
70% of responses were ongoing at the time of data cut-off, demonstrating durability as DOR continues to mature.
BOT/BAL showed a superior benefit-risk profile at 75 mg compared to BOT/BAL 150mg and has been selected for Phase 3 trials.
No new safety signals were observed, and no treatment related deaths occurred. The most common imAEs at BOT 75mg + BAL included diarrhea/colitis (35%) and hypothyroidism (13%).
"The Phase 2 results highlight the unique and consistent activity of the botensilimab and balstilimab combination, demonstrating a compelling objective response rate in microsatellite stable metastatic colorectal cancer, a disease where responses to immunotherapy have historically been absent," said Dr. Marwan Fakih, Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center. "These findings underscore the potential of botensilimab and balstilimab combination treatment in addressing this critical unmet need, paving the way for further investigation."

Gastric Cancer

Phase 2 BOT/BAL/AgenT-797 in Combination with Ramucirumab and Paclitaxel in Patients with Previously Treated, Unresectable or Metastatic Gastroesophageal Cancers (Abstract TPS515):
The Phase 2 trial (NCT06251973) is investigating a novel combination approach, which leverages cellular therapy and immune modulation to address the unmet needs in gastroesophageal cancers. Gastroesophageal cancers continue to be a growing global burden responsible for nearly 1.3 million global deaths annually2.
The novel approach demonstrated early signals of activity and tolerability in the second-line treatment setting, with additional efficacy data anticipated in 2H 2025.
Future Development Plans

Agenus has developed registrational enabling trials in MSS CRC across neoadjuvant, first-line, and late-line settings. These trials will launch upon completion of strategic transactions. Upon the options being considered are, partnerships, licensing, or joint ventures. These initiatives aim to accelerate global access to BOT/BOL to deliver transformative patient outcomes and drive substantial value for stakeholders.

Botensilimab, balstilimab, and agenT-797 are investigational agents and are not approved for use as therapies in any jurisdiction worldwide.

For additional data and publications, visit agenusbio.com/publications.

On January 22, 2025 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 study on the durability of response from the first and largest post-commercialization study of JELMYTO (mitomycin) for pyelocalyceal solution (Press release, UroGen Pharma, JAN 22, 2025, View Source [SID1234649829]). The long-term study evaluated 56 patients who achieved complete response after treatment with JELMYTO from 15 high-volume academic and community centers and helps characterize how urologists are now using JELMYTO in their practices. This long-term study titled, "Durability of Response of UGN-101: Longitudinal Follow-Up of Multicenter Study," is published online in Urologic Oncology: Seminars and Investigations.

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"The three-year durability data from this study further validate the potential of JELMYTO in providing long-term disease control for patients with low-grade upper tract urothelial cancer," said Solomon L. Woldu, MD, Assistant Professor of Urology, UT Southwestern Medical Center, Dallas, Texas, and study investigator. "Notably, we found that recurrence-free survival was not influenced by factors like tumor size or location, highlighting the broad applicability of this treatment. The potential benefits of maintenance therapy are encouraging, and further research will be key in confirming its role in improving outcomes for these patients."

In this study on durability of response, 68% of patients with LG-UTUC who initially responded to JELMYTO had no evidence of disease recurrence at 3 years, as evaluated via endoscopy. The median follow-up was 23.5 months. RFS did not vary significantly based on use of JELMYTO for chemoablative versus adjuvant intent, tumor location (pyelocalyceal versus ureteral), tumor size before induction, single versus multiple tumors, or JELMYTO administration route (antegrade versus retrograde). The administration of maintenance treatment did appear to be associated with significantly better RFS, however, only 15 patients received maintenance therapy and, according to the authors, further study is required to determine the value of maintenance treatments.

"We are excited by the three-year results showing the durability of JELMYTO in treating low-grade upper tract urothelial cancer, with 68% of patients remaining recurrence-free," said Mark Schoenberg, M.D., Chief Medical Officer, UroGen. "These findings underscore the promising long-term potential of JELMYTO in managing this challenging disease. We are committed to improving the lives of patients with urothelial cancer and advancing our mission to deliver breakthrough therapies that transform the standard of care for patients with complex urological conditions."

The limitations of this study include the retrospective design, lack of a control group, and the lack of a centralized pathology review. Further study is needed to better understand the long-term outcomes of JELMYTO and the risks/benefits of maintenance therapy in this setting. In the phase 3 OLYMPUS study, the safety and efficacy of JELMYTO was not investigated in the adjuvant setting (although tumor debulking was permitted prior to study entry), patients with ureteral tumors and tumors larger than 15 mm were excluded, administration was limited to the retrograde technique, and complete response to treatment was assessed via urine cytology, ureteroscopy and biopsy (when warranted). Due to the risks associated with JELMYTO treatment following endoscopic ablation of UTUC or following placement of a nephrostomy tube for JELMYTO instillation (antegrade administration), an appropriate time interval consistent with institutional guidelines and standard medical practice should precede treatment with JELMYTO.

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.