On February 26, 2025 Plus Therapeutics, Inc. (Nasdaq: PSTV) (the "Company" or "Plus Therapeutics"), a clinical-stage pharmaceutical company developing targeted radiotherapeutics with advanced platform technologies for central nervous system (CNS) cancers, reported the completion of the ReSPECT-LM Phase 1 single-dose escalation trial, having determined an RP2D (Press release, Plus Therapeutics, FEB 26, 2025, View Source [SID1234650646]).

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 ReSPECT-LM single-dose escalation trial assessed the safety, tolerability, and potential efficacy of intrathecally administered Rhenium (186Re) Obisbemeda in patients with leptomeningeal metastases (LM). Enrollment in Cohort 6 was recently completed (75.0 mCi). The Cohort 4 dose (44.1 mCi) was determined to be the RP2D; no dose-limiting toxicities were observed at this dose level. One patient at the Cohort 4 dose was observed to have achieved a complete response, as evidenced by the eradication of tumor cells in the cerebrospinal fluid—a key therapeutic endpoint.

"With the RP2D established, we are advancing both a single dose-expansion Phase 2 trial and a multiple-dose Phase 1 trial of 44.1 mCi fractionated into three doses to further assess safety and efficacy," said Marc H. Hedrick, M.D., Plus Therapeutics President and Chief Executive Officer. "We remain on track to complete enrollment in both trials this year and are simultaneously engaging the U.S. Food & Drug Administration to define the optimal pivotal trial pathway."

Additional details on the ReSPECT-LM trial can be found here.

About Leptomeningeal Metastases (LM)

LM is a rare complication of cancer in which the primary cancer spreads to the cerebrospinal fluid (CSF) and leptomeninges surrounding the brain and spinal cord. All malignancies originating from solid tumors, primary brain tumors, or hematological malignancies have this LM complication potential with breast cancer as the most common cancer linked to LM, with 3-5% of breast cancer patients developing LM. Additionally, lung cancer, GI cancers and melanoma can also spread to the CSF and result in LM. LM occurs in approximately 5% of people with cancer and is usually terminal with 1-year and 2-year survival of just 7% and 3%, respectively. The incidence of LM is on the rise, partly because cancer patients are living longer and partly because many standard chemotherapies cannot reach sufficient concentrations in the spinal fluid to kill the tumor cells, yet there are no FDA-approved therapies specifically for LM patients, who often succumb to this complication within weeks to several months, if untreated.

On February 26, 2025 Imugene Limited (ASX: IMU), a clinical-stage immuno-oncology company, reported receipt of a Notice of Allowance from the Chinese Patent Office, for City of Hope’s patent application number 201880064280.9 which protects the CD19-expressing oncolytic virus, onCARlytics (Press release, Imugene, FEB 26, 2025, View Source [SID1234650549]).

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 patent, titled "ONCOLYTIC VIRUS EXPRESSING A CAR T CELL TARGET AND USES THEREOF" protects the method of composition and method of use of onCARlytics through to 2038.

Exclusively licensed to Imugene, OnCARlytics is a CD19-expressing oncolytic virus that enters solid tumour cells and forces them to express the CD19 protein on the cell surface, presenting a target for CD19 targeting therapies.

Imugene’s OASIS dose escalation trial of onCARlytics is being conducted at up to ten sites in the United States, with up to approximately 40 patients proposed to take part in the trial.

Imugene MD & CEO Leslie Chong said: "Intellectual property has remained a priority for our innovative range of immuno-oncology assets, and to have onCARlytics protected in a major market like China is an integral part of this strategy."

On February 26, 2025 Kairos Pharma, Ltd. (NYSE American: KAPA), a clinical-stage biopharmaceutical company, reported that the company presented preclinical data on its investigational compounds KROS 101 and KROS 401 during the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Immuno-Oncology (AACR IO) conference held in Los Angeles from February 23-26, 2025 (Press release, Kairos Pharma, FEB 26, 2025, View Source [SID1234650631]). The data highlighted positive preclinical outcomes with the Company’s glucocorticoid-induced tumor necrosis factor receptor (GITR) agonist KROS101 in melanoma and glioblastoma as well as its peptide inhibitor for macrophages KROS 401 in glioma animal models.

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!

In the presentation, titled "KROS 101: A Next Generation GITR agonist boosting anti-tumor T cell responses and reprogramming the tumor environment," study authors demonstrated that KROS significantly inhibited tumor growth in a preclinical melanoma model. The same team of scientists also showed that KROS 101 increased the proliferation of helper and cytotoxic T cells (CD4+ and CD8+), while decreasing T reg cell growth in a melanoma model. Further, T cells treated with KROS 101 showed cytotoxicity against glioblastoma cell lines and glioma cancer cells, which study authors, Admasu, et. al., concluded KROS 101 demonstrated potent anti-tumor activity compared to a previously used antibody against the GITR receptor TRX518 that was in clinical trials. Most importantly, the authors demonstrated KROS 101 but not TRX518 to prevent the exhaustion of T cells in the tumor.

The second presentation, titled "Targeting M2 macrophage polarization: The anti-tumor effects of IL-4/IL-13 blocking peptide and iron oxide nanoparticles," demonstrated the Company’s peptide inhibitor KROS 401 may effectively reprogram macrophages — types of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances – to inhibit tumor growth. The preclinical study demonstrated that KROS 401 exhibited an anti-tumor effect in glioma-bearing mice following a decrease in M2 macrophages, which are known to facilitate tumor growth.

Dr. John Yu, CEO of Kairos Pharma and co-inventor, commented, "We continue to receive validation of our preclinical data demonstrating our KROS platform’s development of anti-tumor therapies. KROS 101 addresses an Achille’s heel of all T cell immunotherapies and that is the development of exhaustion in anti-tumor T cells. KROS 101 appears to prevent the development of exhaustion by T cells enabling them to continue to kill tumor cells."

Dr. Ram Murali, VP of Research and Development stated, "KROS 401 is designed to reverse the M1 to M2 transition of macrophages in the tumor microenviroment. What this translates to is changing pro-tumor macrophages into anti-tumor macrophages. This leads to tumor-killing activity by both macrophages and T cells."

The American Association for Cancer Research (AACR) (Free AACR Whitepaper) Immuno-Oncology (AACR IO) encompasses the very best of basic, translational, and clinical research in immunology, inflammation, and immunotherapies for cancer, including immuno-oncology (IO) drugs, inflammatory modulators, vaccines, and cellular therapies. The cutting-edge AACR (Free AACR Whitepaper) IO 2025 program will appeal to a wide audience of basic scientists, translational researchers, clinical investigators, regulators, industry, investors, and lay press. A mix of keynote lectures, major symposia, spotlight sessions, educational sessions, special sessions, and poster sessions with exhibits will cover the spectrum of the IO field—including late-breaking clinical trials sessions highlighting new agents and IO combinations, and the results of practice-changing clinical trials.

On February 26, 2025 Agenus Inc. (Nasdaq: AGEN), a leader in immuno-oncology innovation, reported key scientific contributions in 2024-2025 that are shaping the future of cancer immunotherapy (Press release, Agenus, FEB 26, 2025, View Source [SID1234650647]).

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!

Agenus is advancing a robust clinical pipeline targeting complementary mechanisms to fight cancer, including checkpoint inhibitors, immune activators, tumor microenvironment conditioning agents and cell therapies (via MiNK Therapeutics). Our most advanced antibody candidates, botensilimab (BOT) an Fc-enhanced CTLA-4 blocking antibody, and balstilimab (BAL), a novel, PD-1 inhibitor, are central to our efforts.

Driving Innovation of Cancer Immunotherapy

BOT has demonstrated differentiated mechanisms to enhance T cell priming, activation, and memory to drive a more effective immune response and was intentionally designed to mitigate toxicities associated with first-generation anti-CTLA-4 therapies.
BOT is currently being investigated as a monotherapy and in combination with widely used standard of care anti-PD-1, chemotherapy, and allogeneic cell therapy across multiple indications:
MSS colorectal cancer (CRC), pancreatic cancer (in combination with chemotherapy), and gastroesophageal (in combination with BAL and agent-797).
To date, BOT, either alone or in combination with BAL, has been evaluated in approximately 1,100 patients across more than 60 centers worldwide.
The combination targets complementary pathways and has demonstrated clinical responses across nine tumor types, including those historically considered immuno-oncology (IO) "cold" tumors or resistant to prior IO treatments.
Recent data presented at leading international conferences (ASCO, ESMO (Free ESMO Whitepaper), ASCO (Free ASCO Whitepaper) GI, AACR (Free AACR Whitepaper) IO) and featured in prestigious journals (Nature Medicine, Journal of Clinical Oncology, Cancer Discovery), showcase Agenus’ pivotal role in advancing IO research and expanding the reach of IO therapies to new patient populations.

Agenus’ Commitment to Advancing Immuno-Oncology Therapies

"The breadth and consistency of data we have presented over the past year reinforce the transformative potential of botensilimab and balstilimab in redefining treatment paradigms for patients battling historically treatment-resistance cancers. Decades of immuno-oncology research have set the stage for next-generation breakthroughs, and these latest findings with botensilimab and balstilimab represent a major advancement," said Dr. Steven O’Day, Chief Medical Officer, Agenus.

Dr. O’Day continues, "By leveraging our deep expertise in immune activation, we are unlocking responses in tumors previously resistant to immunotherapy. The results are even more promising as we move from treatment refractory metastatic disease to the neoadjuvant setting where we have the potential to reduce the need for adjuvant chemotherapy, preserve organs, and improve long-term survival. These results highlight an opportunity to reshape treatment paradigms and address the greatest unmet needs in oncology."

Breakthrough Findings Across Multiple Cancers

1. Colorectal Cancer:

Neoadjuvant Botensilimab Plus Balstilimab in Resectable Mismatch Repair Proficient (pMMR) and Deficient (dMMR) Colorectal Cancer (CRC) – NEST Study1 link

Conference: ASCO (Free ASCO Whitepaper) GI 2025
Lead Author: Dr. Erika Hissong, Weill Cornell Medicine
Key Findings: This investigator-initiated Phase 2 trial assessed BOT/BAL as neoadjuvant therapy in localized pMMR/MSS and dMMR/MSI-H CRC patients. The combination achieved high major pathological response (MPR) rates, and after median follow-up of 18 months (NEST-1) and 9 months (NEST-2) no recurrences were observed. Extended time to surgery correlated with improved pathological response. The study underscores the potential of dual checkpoint inhibition in neoadjuvant settings for CRC and the potential for non-surgical approaches for some patients​.

Neoadjuvant Botensilimab Plus Balstilimab in Resectable Mismatch Repair Proficient (pMMR) and Deficient (dMMR) Colorectal Cancer (NEST-1 Trial)2 link

Conference: ESMO (Free ESMO Whitepaper) GI 2024
Lead Author: Dr. Pashtoon Kasi (presented by Dr. Mehraneh Jafari), Weill Cornell Medicine
Key Findings: This investigator-initiated Phase 2 trial assessed BOT/BAL as neoadjuvant therapy in resectable pMMR and dMMR colorectal cancer (CRC). A major pathological response (MPR) rate was observed across both cohorts, with no recurrences reported to date. Notably, extended time to surgery was associated with improved responses. Updated data was presented in 2025.

Preoperative Botensilimab (BOT) with or without Balstilimab (BAL) in Resectable, Locally Advanced pMMR or dMMR Colon Cancer – UNICORN Trial3 link

Conference: ASCO (Free ASCO Whitepaper) GI 2025
Lead Author: Dr. Filippo Ghelardi, Fondazione IRCCS Istituto Nazionale dei Tumori Milan
Key Findings: The Investigator-initiated Phase 2 UNICORN trial, explored short-course neoadjuvant BOT ± BAL in non-metastatic CRC patients. Results showed that the addition of BAL significantly enhanced response rates compared to BOT monotherapy, particularly in pMMR tumors. The pCR rate for the combination was 29% and 93% for pMMR and dMMR status, respectively, supporting the potential for non-operative management strategies in CRC​.

Phase 2 Botensilimab Plus Balstilimab in Refractory Microsatellite Stable (MSS) Metastatic Colorectal Cancer with No Liver Metastases4 link

Conference: ASCO (Free ASCO Whitepaper) GI 2025
Lead Author: Dr. Marwan G. Fakih, City of Hope Comprehensive Cancer Center
Key Findings: A Phase 2 study demonstrated deep and durable responses in MSS mCRC patients, demonstrating reproducible response rates (19%) and disease control rate (DCR) of 55% in this refractory metastatic CRC patient population; the standard of care arm had no responses. Notably, some patients treated with BOT/BAL exhibited no active disease over two years after starting the trial.

Phase 1 Study of Botensilimab Plus Balstilimab in Relapsed/Refractory Microsatellite Stable (MSS) Metastatic Colorectal Cancer5 link

Publication: Nature Medicine (September 2024)
Lead Author: Dr. Andrea J. Bullock, Beth Israel Deaconess Medical Center
Key Findings: This study evaluated BOT/BAL in heavily pretreated MSS mCRC patients, a historically checkpoint inhibitor-resistant tumor type. The ORR was 17%, and DCR reached 61%. The combination demonstrated durable responses with a manageable safety profile. In patients with non-active liver metastases (NLM) (n = 77), the ORR was 22% and the DCR was 73% with a 12-month OS rate of 69%. Conversely, in patients with active LM (n=24), ORR was 0% and the DCR was 25% with a 12-month OS rate of 30%. Learnings from this study helped define the P2 study population in MSS mCRC NLM.

A Phase I Trial of FOLFOX-3B: A Combination of Chemotherapy, VEGF(R) Inhibitors, and Checkpoint Blockade in MSS Metastatic Colorectal Cancer6 link

Conference: ASCO (Free ASCO Whitepaper) GI 2025
Lead Author: Dr. Marwan G. Fakih, City of Hope Comprehensive Cancer Center
Key Findings: This Phase I study evaluated the combination of BOT, BAL, FOLFOX chemotherapy, and bevacizumab in MSS metastatic CRC. Preliminary findings showed activity of the combination independent of liver metastases. The regimen demonstrated a 71% objective response rate (ORR) overall. 12/14 patients were pre-treated (FOLFOX "rechallenge"). The combination was well tolerated with only 1/14 patients having immune mediated diarrhea/colitis. Findings suggest that checkpoint blockade plus chemotherapy may enhance immunogenicity in MSS CRC and extend benefit to patients with liver metastases, warranting further investigation in the first line metastatic setting.

2. Gastroesophageal Cancer:

Biomarker Analysis from Phase 2 Study of agenT-797, Botensilimab Plus Balstilimab in PD-1 Refractory Gastroesophageal Cancer link

Conference: AACR (Free AACR Whitepaper) IO 2025
Lead Author: Dr. Samuel L. Cytryn, Memorial Sloan Kettering Cancer Center
Key Findings: This investigator-initiated Phase 2 trial demonstrated significant immune modulation, including robust tumor T-cell infiltration and increased activation of effector-memory T cells, suggesting the potential for overcoming PD-1 resistance.7

3. Sarcoma:

Botensilimab Plus Balstilimab in Relapsed/Refractory (R/R) Metastatic Sarcomas8 link

Publication: Journal of Clinical Oncology (January 2025)
Lead Author: Dr. Breelyn A. Wilky, University of Colorado Cancer Center
Key Findings: This Phase 1 study demonstrated promising efficacy of BOT in combination with BAL, in heavily pretreated sarcoma patients, including soft tissue sarcoma subtypes considered immunologically "cold". Notably, the overall response rate (ORR) was 19.2%, with a 27.8% ORR among angiosarcoma patients. The disease control rate (DCR) reached 65.4%, with a median progression-free survival (PFS) of 4.4 months and a 12-month overall survival (OS) rate of 69%.

Updated Efficacy and Safety of Botensilimab Plus Balstilimab in Metastatic Sarcoma9 link

Conference: ESMO (Free ESMO Whitepaper) 2024
Lead Author: Dr. Breelyn A. Wilky, University of Colorado Cancer Center
Key Findings: Data from an expanded Phase 1 study reaffirmed the activity of BOT/BAL across refractory metastatic sarcomas, including angiosarcoma and leiomyosarcoma. ORR reached 19.2%, with durable responses beyond 21 months in some patients.

4. Mechanistic Insights

Botensilimab, an Fc-Enhanced Anti–CTLA-4 Antibody, Is Effective against Tumors Poorly Responsive to Conventional Immunotherapy10 link

Publication: Cancer Discovery (December 2024)
Lead Author: Dr. Dhan Chand, Agenus Inc.
Key Findings: This landmark study highlighted how botensilimab’s unique design and Fc-enhancement overcomes the limitations of conventional checkpoint inhibitors through multiple immune-activating mechanisms. The research demonstrates that botensilimab potentiates T-cell responsiveness, reduces regulatory T cells, and enhances antigen-presenting cell activation across both preclinical models and patient samples. Clinical data showed significant efficacy in multiple treatment-refractory cancers, including those that progressed on prior immunotherapies. The findings establish a new mechanistic paradigm for expanding immunotherapy benefits to patients with traditionally immunotherapy-resistant cancers.

AGEN1721 – a first-in-class Fc-enhanced Bifunctional Antibody Targeting FAP and TGFβ, Remodels the Tumor Microenvironment to Overcome Cancer-associated Fibroblast-mediated Immune Suppression11 link

Conference: SITC (Free SITC Whitepaper) 2024
Lead Author: Dr. Priya Iyer, Agenus Inc.
Key Findings: AGEN1721, a novel dual-targeting agent, demonstrated the ability to modulate the tumor stroma, enhancing T-cell infiltration and antitumor responses in preclinical models. These findings provide a strong rationale for clinical development.

Additional updates in mCRC, NSCLC, melanoma, ovarian and pancreatic cancer are anticipated in the second half of 2025.

For further details on these studies, please visit www.agenusbio.com, www.minktherapeutics.com or access the respective publications and conference presentations.

On February 26, 2025 Starpharma (ASX: SPL, US OTC: SPHRY), an innovative biotechnology company with two decades of experience in advancing dendrimer technology from the lab to the patient, reported its Interim Report and Half-Year Financial Results for the period ended 31 December 2024 (H1 FY25) (Press release, Starpharma, FEB 26, 2025, View Source;mc_eid=bf52dd3418 [SID1234650550]).

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!

Starpharma’s Chief Executive Officer, Cheryl Maley, commented:

"In the first half of FY25, Starpharma has made good progress in executing our strategy, aimed at maximising the value of our DEP assets, accelerating early asset development, and building long-term sustainability. I know our internal progress may not always be evident externally, but I can vouch for the dedication and hard work of everyone at Starpharma as we work towards achieving our strategic objectives.

"We have made important progress in advancing our DEP clinical assets, particularly DEP SN38, which has shown promising clinical outcomes in patients with high unmet need. A key regulatory milestone during the period was the recent meeting with the US Food and Drug Administration (FDA) regarding DEP SN38. The FDA provided feedback on the path to market for DEP SN38, confirming that the 505(b)(2) regulatory approval pathway is appropriate for DEP SN38 and the potential for Fast Track designation and accelerated approval. The positive response from the US regulator increases our confidence in the potential of DEP SN38 for treating platinum-resistant ovarian cancer. During the six months to December, our partner engagement through ongoing meetings and conference participation highlighted the importance of FDA feedback to potential partners for the commercialisation of DEP SN38.

"We are advancing our early-stage DEP programs, particularly in the area of radiopharmaceuticals, with the aim of initiating a first-in-patient clinical trial this calendar year. We are also expanding our research pipeline, positioning us well for future collaborations and long-term growth. Commercially, we anticipate the launch of VivaGel BV in key markets in the Middle East and continue to support sales of Viraleze online through digital marketing initiatives, which have resulted in a ~30% increase in revenue from the e-commerce channels compared to the prior corresponding period.

"We have focused on building a sustainable organisation and have sufficient capital to support our medium-term objectives, with a cash balance of $20.3 million as at 31 December 2024. The completion of multiple clinical programs in FY24 has led to a reduction in our research and development expenses, extending our cash runway. Over the past 12 to 18 months, we have implemented a number of cost-saving initiatives that are positively impacting our cash balance. Notably, our Corporate and Administration costs in this half-year period have decreased by $0.5 million compared to the prior corresponding period.

"Starpharma is committed to driving revenue growth, advancing our pipeline, and managing costs effectively to deliver improved and long-term value for our shareholders. We are focused on prioritising resources for our high-impact DEP programs, pursuing partnerships to advance our assets toward commercialisation, and increasing revenue through collaborations, licensing and product sales."