On April 29, 2025 Pilatus Biosciences, a biotechnology company developing immunometabolic therapies for cancer, reported a preclinical publication in Cancer Discovery detailing the mechanism and therapeutic potential of its lead candidate, PLT012 (Press release, Pilatus Biosciences, APR 29, 2025, View Source [SID1234652340]).

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The paper, titled: "PLT012, a Humanized CD36-Blocking Antibody, Is Effective for Unleashing Anti-Tumor Immunity Against Liver Cancer and Liver Metastasis," establishes PLT012 as the first humanized antibody to target CD36, a lipid scavenger receptor implicated in immune dysfunction in metabolically hostile tumor microenvironments and highlights its efficacy in restoring anti-tumor immunity in hepatocellular carcinoma (HCC) and colorectal liver metastases.

CD36 is upregulated in immune cells exposed to lipid-rich, inflammatory environments and has emerged as a key driver of immune suppression in solid tumors. By blocking CD36-mediated lipid uptake, PLT012 reduces intratumoral Tregs and pro-tumor macrophages, while enhancing CD8+ T cell infiltration, survival, and cytotoxicity.

"Liver cancer presents a unique opportunity to improve patient outcomes by addressing the underlying immunometabolic suppression that can limit the effectiveness of current checkpoint inhibitors," said Yi-Ru Yu, Ph.D., Lead Scientist of Pilatus Biosciences and co-first author of the study. "Our data show that PLT012, our lead CD36-targeting immunometabolic therapy, restores immune function at its metabolic core to reprogram the tumor environment to enable effective and durable anti-tumor responses."

Key Findings from the Cancer Discovery Study:

PLT012 monotherapy drives tumor regression in both immune-inflamed and immune-excluded HCC models, including β-catenin–driven tumors resistant to checkpoint blockade.
In combination with anti-PD-L1 and anti-VEGF therapies, PLT012 significantly improves tumor control and increases complete response rates.
In colorectal cancer models with liver metastases, PLT012 restores responsiveness to PD-1 blockade and reprograms macrophage phenotypes.
Ex vivo validation in human HCC samples showed increased CD8+ T cell activity in 45% of patient samples and decreased Tregs in 82% of samples treated with PLT012.
Toxicology studies in non-human primates confirmed a favorable safety profile, with no adverse effects observed at doses up to 200 mg/kg.
"This work validates CD36 as a tractable target in immuno-oncology and positions PLT012 as a first-in-class therapeutic with broad potential across solid tumors characterized by metabolic immune suppression," said Raven Lin, CEO & Founder, Pilatus Biosciences. "These important milestones highlight PLT012’s potential to transform treatment for patients with advanced solid tumors."

"The ability of PLT012 to reprogram the tumor microenvironment by overcoming metabolic immune suppression marks a major advancement for the field of immuno-oncology," said Ping-Chih Ho, Ph.D., Co-Founder and Chair of the Scientific Advisory Board at Pilatus Biosciences, who presented the data as an oral presentation at AACR (Free AACR Whitepaper) 2025. "Our findings validate CD36 as a novel immunometabolic target and demonstrate the broad potential of PLT012 to restore effective anti-tumor immunity across solid tumors. I look forward to seeing Pilatus bring this important new therapeutic approach into clinical development."

PLT012 has received FDA Orphan Drug Designation for the treatment of HCC and intrahepatic bile duct cancer, reinforcing its potential to address rare, aggressive liver malignancies with limited treatment options. Pilatus is advancing PLT012 through IND-enabling studies, with plans to file an IND by end of 2025 to initiate clinical development next year.

About PLT012

PLT012 is a humanized monoclonal antibody designed to selectively block CD36-mediated lipid uptake, a key mechanism driving immunosuppression and immune exclusion within the tumor microenvironment. PLT012 simultaneously reduces Tregs and pro-tumor macrophages while enhancing anti-tumor activities of intratumoral NK cell and cytotoxic CD8+ T cell. The antibody has demonstrated potent monotherapy and combination activity in preclinical models of HCC, liver metastases, and high-fat-diet–induced tumor progression, with a favorable safety profile across species.

On April 29, 2025 Bicycle Therapeutics plc (NASDAQ: BCYC), a biopharmaceutical company pioneering a new and differentiated class of therapeutics based on its proprietary bicyclic peptide (Bicycle) technology, reported the presentation of additional human imaging data that validate the potential of MT1-MMP, a tumor antigen overexpressed in many cancers, as a novel target for cancer treatment and demonstrate the positive properties of Bicycle Radioconjugates (BRC) for radiopharmaceutical imaging (Press release, Bicycle Therapeutics, APR 29, 2025, View Source [SID1234652303]). The data will be presented today during a poster session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025 in Chicago.

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"The additional imaging data using an early BRC molecule continue to validate the potential of MT1-MMP as a novel cancer target, demonstrate the translatability of our preclinical data and position our technology for use as potential radiopharmaceutical therapies," said Michael Skynner, Ph.D., chief technology officer of Bicycle Therapeutics. "The new imaging data from the second patient with breast and bladder cancer presented today build on what was previously demonstrated in the first patient with advanced lung cancer, and we are encouraged that these data represent what we have seen so far in 12 patients with various solid tumors. We continue to advance our radiopharmaceuticals pipeline and look forward to sharing additional updates in the future, including initial human imaging data for our second target EphA2 later this year and the start of our first company-sponsored clinical radiopharmaceutical trials next year."

AACR 2025 Data Highlights

The German Cancer Consortium (DKTK), part of a cooperative network with the German Cancer Research Center (DKFZ), will present human imaging data conducted with an early BRC molecule targeting MT1-MMP. Imaging was performed in a 65-year-old male diagnosed with advanced pulmonary adenocarcinoma, the most common type of non-small cell lung cancer, and an 84-year-old female diagnosed with invasive ductal breast cancer and high-grade urothelial (bladder) cancer.

The 65-year-old male patient with advanced pulmonary adenocarcinoma underwent fluorine-18-labelled FDG-PET/CT imaging and two weeks later underwent MT1-MMP-PET/CT imaging up to one hour post injection of the gallium-68-labelled BRC tracer. As presented at a previous medical meeting, the MT1-MMP-PET scan demonstrated BRC tracer uptake in the primary tumor in the lung and in the lymph nodes and bones where the cancer had spread, corroborating the findings of the FDG-PET scan. While MT1-MMP-PET imaging demonstrated lower BRC tracer uptake in the primary tumor compared to FDG-PET imaging [maximum standardized uptake value (SUVmax) 6.0 g/mL vs. 10.3 g/mL], MT1-MMP-PET BRC tracer uptake was comparable in lymph node metastases (SUVmax 4.7 g/mL vs. 4.4 g/mL) and higher in bone metastases (SUVmax 7.9 g/mL vs. 6.0 g/mL).

The 84-year-old female patient with invasive ductal breast cancer and high-grade urothelial cancer underwent contrast-enhanced CT imaging and later underwent MT1-MMP-PET/CT imaging up to one hour post injection of the gallium-68-labelled BRC tracer. The MT1-MMP-PET scan revealed higher BRC tracer uptake in the primary tumors in the breast (SUVmax 4.5 g/mL) and the bladder (SUVmax 6.6 g/mL) compared to contrast-enhanced CT imaging. The MT1-MMP-PET scan also showed the cancer spread to the lymph nodes, lower spine (sacral bone) and skull, and detected a mass in the adrenal gland above the left kidney. Surgery confirmed the patient had bladder cancer that spread to the lymph nodes, and immunohistochemistry (IHC) testing confirmed MT1-MMP expression in the tumor cells.

These data are representative of the results seen in 12 out of 14 patients with various cancers, including those affecting the lung, head and neck, and bladder, who have undergone MT1-MMP-PET imaging to date. Imaging was unsuccessful or inconclusive in two patients. Overall, the results demonstrate the rapid distribution of the BRC tracer throughout the body, high uptake of the BRC tracer in the primary tumor(s) and/or in metastases where the cancer spread in the body, and elimination through the kidneys. Scans showing retention in the kidneys were in line with expectations given the imaging was conducted using a pathfinder non-optimized BRC imaging agent. Additional and more detailed analyses of the data and confirmation of MT1-MMP expression in the tumors via IHC are ongoing.

The poster presentation, "Development and clinical translation of phage display derived MT1-MMP-specific bicyclic peptide for radiotheranostic applications," is available in the Publications section of the Bicycle Therapeutics website.

On April 29, 2025 Shorla Oncology (‘Shorla’), a U.S.-Ireland specialty pharmaceutical company, reported that the U.S. Food and Drug Administration has granted approval for 100 mg/10mL multi-dose vial of TEPYLUTE, a ready-to-dilute formulation of thiotepa to treat breast and ovarian cancer, that eliminates the need for reconstitution and may reduce preparation time and errors offering more scheduling flexibility for their patients (Press release, Shorla Oncology, APR 29, 2025, View Source [SID1234652341]).

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"We are pleased to offer another viable treatment option for patients with breast and ovarian cancer," said Sharon Cunningham, Chief Executive Officer and Co-Founder of Shorla Oncology. "Once opened, our 100mg vial of TEPYLUTE is stable for 14 days when properly stored, giving providers the flexibility they need when preparing and administering this very important treatment.

TEPYLUTE is a ready to dilute formulation of a well-established, standard of care oncology drug thiotepa that has been manufactured as freeze-dried powder since the 1950s.

"This is a huge win for providers because TEPYLUTE avoids the need for complicated and time-consuming reconstitution," said Orlaith Ryan, Chief Technical Officer and Co-Founder of Shorla Oncology.

We are excited to bring TEPYLUTE to the US Market. It provides consistent dosing accuracy and allows for "just in time" preparation, which benefits everyone, especially patients." said Rayna Herman, Chief Commercial Officer, Shorla Oncology.

The American Cancer Society estimates that more than 300,000 women will be diagnosed with breast cancer in the U.S in 2025.2 About 20,890 women will be diagnosed with ovarian cancer in the U.S. in 2025.

On April 29, 2025 Blacksmith Medicines, Inc. (Blacksmith), a leading biopharma dedicated to discovering and developing therapeutics targeting metalloenzymes, reported the company will present data on its oncology program targeting flap endonuclease 1 (FEN1), a structure-specific metallonuclease that cleaves 5′ DNA flaps during replication and repair, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025, taking place April 25-30 at the McCormick Place Convention Center, Chicago, IL (Press release, Blacksmith Medicines, APR 29, 2025, View Source [SID1234652304]).

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Details of the poster presentation are as follows:

Abstract Number: 5720
Title: "Novel FEN1 nuclease inhibitor shows synergy with PARP-targeting drugs"
Session Category: Experimental and Molecular Therapeutics
Session Title: PARP Inhibitors
Session Date and Time: Tuesday April 29, 2025 2:00 PM – 5:00 PM
Location: Poster Section 24
Poster Board Number: 7

The abstract is now available on the conference website at AACR (Free AACR Whitepaper) Annual Meeting 2025.

About FEN1
Flap endonuclease 1 (FEN1) is a structure-specific di-magnesium metallonuclease that cleaves 5′ DNA flaps during replication and repair. FEN1 is an attractive target for development of anticancer therapeutics because it is overexpressed in many tumor types and has a large number of synthetic lethality partners including genes in Homologous Recombination (HR) pathway.

About metalloenzymes and the Blacksmith platform
Metalloenzymes utilize a metal ion cofactor in the enzyme active site to perform essential biological functions. This diverse class of targets has historically been difficult to drug due to small molecule chemistry limitations that have plagued the industry. The Blacksmith metalloenzyme platform has solved this problem by leveraging the following:

A large proprietary fragment library of metal-binding pharmacophores (MBPs);
A comprehensive database containing a full characterization of the metalloenzyme genome including functions, metal cofactors, and associations to disease;
A first-of-its-kind metallo-CRISPR library of custom single guide RNAs;
An industry-leading metalloenzyme computational toolkit for docking, modeling and structure-based drug design; and
A robust and blocking intellectual property estate covering bioinorganic, medicinal, and computational chemistry approaches for metalloenzyme-targeted medicines.

On April 29, 2025 Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a fully-integrated biopharmaceutical company with marketed products and a pipeline of development candidates, reported data in a poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2025 Annual Meeting, held April 25-30, 2025, in Chicago, IL (Press release, TONIX Pharmaceuticals, APR 29, 2025, View Source [SID1234652325]). A copy of the Company’s presentation is available under the Scientific Presentations tab of the Tonix website at www.tonixpharma.com. The presentation titled, "TFF2-mediated CXCR4 partial agonism outperforms CXCR4 antagonism in reducing murine gastric cancer by suppressing PMN-MDSC generation," demonstrated positive data in gastric cancer animal models. In the AACR (Free AACR Whitepaper) presentation, a fusion protein of murine trefoil factor family member 2- murine serum albumin (mTFF2-MSA) was studied. Tonix is developing human TFF2-human serum albumin (hTFF2-HAS) as TNX-1700.

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"The combination therapy of mTFF2-MSA with anti-PD1 treatment shows promise in reducing immunosuppression in the tumor microenvironment (TME) in animal models," said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. "We are excited to develop TNX-1700 (TFF2-HAS) as the lead program in our immuno-oncology pipeline, by testing potential dosing strategies, and establishing potential clinical biomarkers through preclinical models."

Immunosuppressive neutrophils, also known as polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), are a major component in solid tumors that significantly hinder anti-tumor activity1,2. Despite being short-lived, their continuous replenishment from the bone marrow sustains their potent immunosuppression in the TME3. Stromal cells in the TME promote immunosuppression by recruiting MDSCs via secretion of CXCL12. Trefoil Factor 2 (TFF2), a secreted peptide of the trefoil factor family, has displayed activity as a partial agonist of CXCR44,5. Data presented in the poster demonstrated that TFF2-MSA selectively reduces immunosuppressive neutrophils and cancer-driven granulopoiesis. Treatment with TFF2-MSA, in combination with an anti-PD1 antibody, induced robust anti-tumoral CD8+ T cell responses, inhibiting tumor invasion. TFF2 reduction correlated with elevated PMN-MDSCs in gastric cancer patients, highlighting the potential negative correlation between TFF2 and PMN-MDSCs levels.

About Trefoil Factor Family Member 2 (TFF2)

Human TFF2 is a secreted protein, encoded by the TFF2 gene in humans, that is expressed in gastrointestinal mucosa where it functions to protect and repair mucosa. TFF2 is also expressed at low levels in splenic immune cells and is now appreciated to have intravascular roles in the spleen and in the tumor microenvironment. In gastric cancer, TFF2 is epigenetically silenced, and TFF2 is suggested to be protective against cancer development through several mechanisms. Tonix is developing TNX-1700 (rTFF2-HSA) for the treatment of gastric and colon cancers under a license from Columbia University. The inventor of the core technology at Columbia is Dr. Timothy Wang, who is an expert in the molecular mechanisms of carcinogenesis whose research has focused on the carcinogenic role of inflammation in modulating stem cell functions. Dr. Wang demonstrated that knocking out the mTFF2 gene in mice leads to faster tumor growth and that overexpression of TFF2 markedly suppresses tumor growth by curtailing the homing, differentiation, and expansion of MDSCs to allow activation of cancer-killing CD8+ T cells. He went on to show that a novel engineered form of recombinant murine TFF2 (mTFF2-CTP) had an extended half-life in vivo and was able to suppress MDSCs and tumor growth in an animal model of colorectal cancer. Later, he showed in gastric cancer models that suppressing MDSCs using chemotherapy enhances the effectiveness of anti-PD1 therapy and significantly reduces tumor growth. Dr. Wang proposed the concept of employing rTFF2 in combination with other therapies in cancer prevention and early treatment.