Clarity receives U.S. FDA Fast Track Designation for Cu-64 SAR-bisPSMA in biochemical recurrence of prostate cancer

On January 24, 2025 Clarity Pharmaceuticals (ASX: CU6) ("Clarity" or "Company"), a clinical-stage radiopharmaceutical company with a mission to develop next-generation products that improve treatment outcomes for children and adults with cancer, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track Designation (FTD) for 64Cu-SAR-bisPSMA for positron emission tomography (PET) imaging of prostate-specific membrane antigen (PSMA) positive prostate cancer lesions in patients with biochemical recurrence (BCR) of prostate cancer following definitive therapy (Press release, Clarity Pharmaceuticals, JAN 24, 2025, View Source [SID1234649847]).

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This milestone builds on Clarity’s earlier receipt of an FTD for 64Cu-SAR-bisPSMA in patients with suspected metastasis of prostate cancer who are candidates for initial definitive therapy1. These 2 FTDs enable the Company to accelerate the development of its comprehensive diagnostic program with this product.

The FDA’s FTD is designed to expedite the development and regulatory review of novel drugs addressing serious conditions with significant unmet medical needs. For 64Cu-SAR-bisPSMA, it provides a number of product development advantages. The designation paves the way for a faster review process once Clarity submits its product approval applications. Additionally, it enables more frequent communication with the FDA, allowing for rapid resolution of queries during development. Furthermore, Clarity can submit completed sections of its application as they are ready, rather than waiting for the entire package to be finished before it can be lodged with the FDA. These benefits would reduce the review time needed to bring this innovative prostate cancer imaging agent to market, potentially improving diagnosis and treatment planning for patients sooner.

The FTD submission highlighted several advantages of 64Cu-SAR-bisPSMA over currently approved PSMA PET agents due to the bivalent structure of bisPSMA and the longer half-life of 64Cu (12.7 hours vs. <2 hours for 18F and 68Ga). These advantages include improved diagnostic performance, flexible imaging schedule and broader availability. The data for this FTD submission was primarily focused on the results of the Phase I/II COBRA study, which assessed the safety and diagnostic performance of 64Cu-SAR-bisPSMA in detecting prostate cancer in patients with BCR of their disease who had a negative or equivocal standard of care (SOC) scan at study entry. Advantages have been shown with same-day and next-day imaging, however, the standout was next-day 64Cu-SAR-bisPSMA PET imaging, showing localised disease in up to 80% of participants and detecting lesions as small as 2 mm. This compares favourably against the current SOC PSMA PET agents, with which the detection of lesions smaller than 5 mm is challenging. The number of lesions detected by 64Cu-SAR-bisPSMA on next-day imaging almost doubled compared to same-day imaging, and 64Cu-SAR-bisPSMA was also able to identify more lesions at much earlier timepoints (Figure 1) compared to approved PSMA PET agents.The COBRA trial paved the way for Clarity’s second diagnostic registrational trial, AMPLIFY, and an investigator-initiated trial (IIT) Co-PSMA, led by Prof Louise Emmett at St Vincent’s Hospital Sydney. The AMPLIFY trial will be a non-randomised, single-arm, open-label, multi-centre, Phase III diagnostic clinical trial of 64Cu-SAR-bisPSMA PET in approximately 220 participants with rising or detectable PSA after initial definitive treatment. As a pivotal trial, the final study results are intended to provide sufficient evidence to support an application to the FDA for approval of 64Cu-SAR-bisPSMA as a new diagnostic imaging agent in prostate cancer in patients with BCR. The Co-PSMA IIT will aim to build on the evidence generated so far, evaluating the diagnostic performance of 64Cu-SAR-bisPSMA in comparison to SOC 68Ga-PSMA-11 for the detection of recurrent prostate cancer lesions with curative intent.

Clarity’s Executive Chairperson, Dr Alan Taylor, commented, "Receiving the second FTD for 64Cu-SAR-bisPSMA and well within the 60-day period following our application submission, reserved by the U.S. FDA for review, is yet another significant milestone in our bisPSMA program. This highlights the high unmet need for novel diagnostics in prostate cancer and the high quality of data we presented to the FDA.

"The market for first-generation diagnostic PSMA PET today is approximately US$2 billion (AU$3.2 billion) in the U.S. alone, with little differentiation between products. It is expected to further grow to US$3 billion (AU$4.75 billion) by 2029. The development pipeline of new products coming to market, outside of 64Cu-SAR-bisPSMA, also offers no differentiation from the existing offering, with some new entrants commercialising the unpatented 68Ga-PSMA-11 agent, which has been capitalised on by three separate groups already.

"Being able to now fast-track the development of 64Cu-SAR-bisPSMA for patients with BCR as well as for patients prior to initial definitive therapy is incredibly exciting. The news is especially timely as we are actively preparing to commence recruitment for our second registrational trial, AMPLIFY, in the coming months. The designation will allow us to work closely with the FDA to facilitate the development process and accelerate the approval of what could become a best-in-class diagnostic.

"The dual targeting structure of bisPSMA enables increased uptake and retention of the product in the lesions, while the longer half-life of copper-64 provides greater flexibility with imaging scheduling, including next-day imaging (something that gallium-68 and fluorine-18 based products cannot support). When combined, these features make 64Cu-SAR-bisPSMA stand out from its competitors who are known to have issues with sensitivity. We have seen 2-3 times higher uptake in prostate cancer lesions and the identification of more lesions using 64Cu-SAR-bisPSMA compared to 68Ga-PSMA-11 in pre-prostatectomy patients in our PROPELLER study. The COBRA trial results showed great diagnostic performance in the BCR setting, with lesions identified by 64Cu-SAR-bisPSMA in the 2-mm range and visualised many months before SOC PSMA PET agents are able detect them.

"Not only are we developing a product that may have improved diagnostic performance compared to SOC PSMA PET agents, but the longer half-life of copper-64 also enables a longer shelf-life of 64Cu-SAR-bisPSMA than currently used diagnostic radiopharmaceuticals, allowing for centralised manufacture and wider distribution. These attributes have the potential to reduce disparities in prostate cancer care and ensure that most patients, regardless of geographic location, can benefit from the latest advances in diagnostic technology.

"This designation highlights the unique opportunity for 64Cu-SAR-bisPSMA in this very large market by addressing the limitations of the current-generation diagnostic radiopharmaceuticals and providing patients with prostate cancer with a more accurate diagnosis leading to more optimal treatment options. As such, we are fully committed to advancing the development of this best-in-class product to address the critical need for more accurate and accessible diagnostic tools in prostate cancer management."

About SAR-bisPSMA
SAR-bisPSMA derives its name from the word "bis", which reflects a novel approach of connecting two PSMA-targeting agents to Clarity’s proprietary sarcophagine (SAR) technology that securely holds copper isotopes inside a cage-like structure, called a chelator. Unlike other commercially available chelators, the SAR technology prevents copper leakage into the body. SAR-bisPSMA is a Targeted Copper Theranostic (TCT) that can be used with isotopes of copper-64 (Cu-64 or 64Cu) for imaging and copper-67 (Cu-67 or 67Cu) for therapy.

About Prostate Cancer
Prostate cancer is the second most common cancer diagnosed in men globally and the fifth leading cause of cancer death in men worldwide4. Prostate cancer is the second-leading causes of cancer death in American men. The American Cancer Institute estimates in 2025 there will be about 313,780 new cases of prostate cancer in the U.S. and around 35,770 deaths from the disease.

Ascentage Pharma Announces Pricing of U.S. Initial Public Offering

On January 23, 2025 Ascentage Pharma (Nasdaq: AAPG) (HKEX: 6855) reported the pricing of its U.S. initial public offering of 7,325,000 American depositary shares ("ADSs"), at a public offering price of $17.25 per ADS, before underwriting discounts and commissions (Press release, Ascentage Pharma, JAN 23, 2025, View Source [SID1234650021]). Each ADS represents four ordinary shares of Ascentage Pharma. The gross proceeds from the offering, before deducting underwriting discounts and commissions and other offering expenses payable by Ascentage Pharma, are expected to be approximately $126.4 million. In addition, Ascentage Pharma has granted the underwriters a 30-day option to purchase up to an additional 1,098,750 ADSs at the initial public offering price, less underwriting discounts and commissions. The ADSs are expected to begin trading on the Nasdaq Global Market on January 24, 2025, under the ticker "AAPGV" on a "when-issued" basis, and on January 27, 2025, under the ticker symbol "AAPG" for "regular-way" trading. The offering is expected to close on January 28, 2025, subject to customary closing conditions.

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J.P. Morgan and Citigroup are acting as joint book-running managers for the offering.

A registration statement relating to these securities was declared effective by the Securities and Exchange Commission on January 23, 2025. The offering will be made only by means of a prospectus. Copies of the prospectus relating to the offering may be obtained, from: J.P. Morgan Securities LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, or by email at [email protected] and [email protected], and Citigroup, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, or by telephone at 1-800-831-9146.

This press release shall not constitute an offer to sell or a solicitation of an offer to buy, 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 registration or qualification under the securities laws of any such state or jurisdiction.

Parabilis Medicines to Present Trial-in-Progress Poster on Phase 1/2 Study of FOG-001, a β-cateninTCF4 Inhibitor, at ASCO Gastrointestinal Cancers Symposium

On January 23, 2025 Parabilis Medicines (formerly Fog Pharmaceuticals), a clinical-stage biopharmaceutical company dedicated to creating extraordinary medicines for people living with cancer, reported the presentation of a trial-in-progress poster on the Company’s first-in-human clinical trial evaluating FOG-001, the first and only direct inhibitor of β-cateninTCF4, at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium taking place in San Francisco from January 23-25, 2025 (Press release, Parabilis Medicines, JAN 23, 2025, View Source [SID1234649861]).

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FOG-001 is being evaluated in a Phase 1/2 clinical trial (NCT05919264). The multicenter, open-label, non-randomized trial aims to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of FOG-001 in patients with microsatellite stable colorectal cancer (MSS CRC) and other solid tumors with Wnt pathway activating mutations (WPAM+). The trial plans to enroll patients in multiple third-line MSS CRC cohorts as both a monotherapy and in combination with FOLFOX+bevacizumab, anti-PD-1/PD-L1, or trifluridine/tipiracil+bevacizumab.

At the 2025 J.P. Morgan Healthcare Conference, Parabilis provided an update on the trial’s progress. The Company disclosed that more than 60 patients with locally advanced or metastatic solid tumors have been dosed with FOG-001 to date, and that early clinical data demonstrate monotherapy antitumor activity and in-tumor target engagement. Preliminary Phase 1/2 data are expected to be shared publicly in 2025.

Full details of the poster are as follows:

Title: "A Phase 1/2 study of FOG-001, a first-in-class direct β-catenin:TCF inhibitor, in patients with colorectal cancer, hepatocellular carcinoma, and other locally advanced or metastatic solid tumors"
Abstract Number: TPS322
Presentation Date and Time: January 25, 2025, 7:00-7:55 a.m. PST
Session Information: Trials in Progress Poster Session C
Location: Level 1, West Hall, Moscone West

About FOG-001
FOG-001 is an investigational first-in-class competitive inhibitor of β-catenin interactions with the T-cell factor (TCF) family of transcription factors, and is currently in clinical development. By directly targeting the β-cateninTCF4 protein-protein interaction, FOG-001 is intended to block the Wnt signaling pathway irrespective of the various APC and beta-catenin mutations that typically drive disease.

FOG-001 combines key features that distinguish it from previously reported Wnt/β-catenin pathway modulators: FOG-001 acts inside the cell where it binds directly to the key oncogenic driver β-catenin; and FOG-001 blocks the Wnt pathway at the most downstream node, disrupting the interaction between β-catenin and the transcription factor TCF, thereby abrogating the signal transmission by which Wnt pathway mutations are believed to drive oncogenesis. FOG-001 is currently being evaluated in a first-in-human Phase 1/2 clinical trial in patients with locally advanced or metastatic solid tumors.

Guardant Health to Present Data at ASCO GI Demonstrating the Value of Its Precision Oncology Tools for Cancer Detection, Treatment Decisions and Therapy Development

On January 23, 2025 Guardant Health, Inc. (Nasdaq: GH), a leading precision oncology company, reported the company and its research collaborators will present data showcasing the benefits of Guardant’s precision oncology tools across cancer screening, recurrence monitoring, treatment selection and therapy development at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium (ASCO GI) in San Francisco, January 23-25, 2025 (Press release, Guardant Health, JAN 23, 2025, View Source [SID1234649860]).

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Key focus areas in Guardant’s co-authored abstracts and collaborator presentations utilizing Guardant products include the impact of mutations on treatment response in colorectal cancer and biliary tract cancers, and additional support for the benefits of blood-based screening in colorectal, gastric and esophageal cancers. A rapid oral presentation will feature data from the phase II NEO trial highlighting Guardant Reveal as a decision tool to support organ preservation in patients with node-negative rectal cancer undergoing neoadjuvant chemotherapy, excision and observation.

"Data increasingly supports the value of precision oncology tools, and specifically liquid biopsy, in detecting GI cancers, informing treatment selection, and monitoring for recurrence and therapy response," said Craig Eagle, MD, Guardant Health chief medical officer. "Findings presented at ASCO (Free ASCO Whitepaper) GI demonstrate the advancements being made by Guardant Health and our partners in these areas and show the potential for these tools to provide even more personalized cancer care, leading to better patient outcomes."

Guardant Health ASCO (Free ASCO Whitepaper) GI 2025 Co-Authored Posters and Presentations

Time and Location

Title

Abstract and

Presentation Type

Guardant Reveal

January 25, 2025

9:15 – 10:00 am PST

Level 2, Ballroom

Tumour-free ctDNA detection as a decision tool to support organ preservation in node-negative rectal cancer undergoing neoadjuvant chemotherapy, excision, and observation in the phase II NEO trial (CCTG CO.28)

Rapid Oral Abstract

Session C

Abstract #20

Guardant360

January 25, 2025

7:00 – 7:55 am PST

Level 1, West Hall

Retrospective study evaluating the genomic landscape of anal squamous cell carcinoma using liquid biopsy

Poster Session C

Abstract #8

Landscape of metastatic colorectal cancer (CRC) using comprehensive circulating tumor DNA (ctDNA) next-generation sequencing (NGS) in India: Expanding beyond RAS and RAF

Poster Session C

Abstract #49

GuardantINFORM

January 24, 2025

11:30 am – 1:00 pm PST

Level 1, West Hall

Real-world survival differences in advanced biliary tract cancer patients with ctDNA detected IDH1 mutations and FGFR2 fusions receiving first-line gemcitabine-cisplatin with and without immunotherapy

Poster Session B

Abstract #548

ShieldTM

January 25, 2025

7:00 – 7:55 am PST

Level 1, West Hall

Cost-effectiveness of blood-based colorectal cancer screening: A simulation model incorporating real-world longitudinal adherence

Poster Session C

Abstract #93

A method for classifying colorectal cancer and gastric/esophageal cancer using blood-based testing

Poster Session C

Abstract #52

The full abstracts for Guardant Health and a list of all abstracts being presented at ASCO (Free ASCO Whitepaper) GI 2025 can be found on the ASCO (Free ASCO Whitepaper) website.

EXUMA Biotech Announces Phase 1 Results for its Autologous HER2 Directed, Tumor Metabolism Regulated (TMR) CAR-T Product at ASCO GI 2025

On January 23, 2025 EXUMA Biotech, Corp., a clinical-stage biotechnology company discovering and developing cell and gene immunotherapies for solid and hematological malignancies, reported clinical data from a completed Phase 1 trial evaluating a novel autologous HER2-targeted CAR-T therapy (Press release, EXUMA Biotech, JAN 23, 2025, View Source [SID1234649859]). The data presented today at the ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium, highlights promising efficacy and safety for autologous engineered human T cells that target cancer via a proprietary chimeric antigen receptor (CAR) designed to selectively target HER2 in the tumor microenvironment (TME).

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The single center, investigator-initiated, dose escalation trial enrolled 12 patients with HER2-positive Stage IV solid tumor malignancies, including three gastric, one esophageal, four colorectal, and four breast cancers. Patients received a single dose of CAR-T cells (3E5, 1E6, or 1E7 CAR+ cells/kg) from a peripheral blood draw-derived 12-day manufacturing process (17 days to product release) following lymphodepletion with cyclophosphamide and fludarabine. No manufacturing failures occurred.

Key Findings:

Safety: No dose limiting toxicities or investigational-product related serious adverse events. No adverse events leading to study discontinuation. One patient experienced Grade 2 cytokine release syndrome (CRS), which resolved. No ICANs or any other CNS toxicities occurred. No on-target, off-tumor toxicity (OTOTT) was detected with longitudinal clinical and laboratory assessments.
Efficacy: A deep PR (100% reduction in SLD) was observed in a gastroesophageal cancer patient that was ongoing at 36 weeks of follow-up. Cohort 3’s 12-month survival rate was 80%, compared to 45.5% for all three dose cohorts combined.
Wendy Li, MD Chief Medical Officer of EXUMA Biotech, remarked, "There continues to be a need for treatments with the potential to safely elicit frequent deep and durable responses in HER2 positive gastroesophageal cancer patients through different mechanisms of action. We administered the maximum feasible dose, which delivered clear anti-tumor activity in patients without OTOTT or dose limiting toxicities. Our team is now focused on patients with HER2 positive gastroesophageal malignancies, particularly in Asia, where the incidence of gastroesophageal cancers contributes significantly to morbidity and mortality."

Abstract Title: Clinical results of a phase 1 trial evaluating a HER2 directed CAR-T product selective for the tumor microenvironment (TME) in patients with GI and other solid tumor malignancies
Abstract ID: 449
Poster #: F14

About CCT303-406
CCT303-406 is EXUMA Biotech’s TMR autologous CAR-T product candidate targeting HER2, which has completed an investigator-initiated clinical trial in patients with metastatic HER2+ solid tumors. HER2 overexpression is a hallmark of several tumors, including those originating from breast, stomach, bladder, and colon. Patients relapse or become unresponsive to antibody-based regimens targeting HER2 in early lines of treatment yet may still retain overexpression of HER2. CCT303-406 has clinically shown to be a promising option for gastroesophageal patients providing T cell-mediated antitumor activity via targeting HER2. Differentiated from other HER2 CAR-T therapies, CCT303-406 incorporates EXUMA’s TMR targeting technology, focusing CAR-T activity to the TME, thereby reducing the risk of on-target, off-tumor toxicity.

GCAR and SCL Update
EXUMA plans to complete non-human primate (NHP) studies in support of its 1st in vivo CAR-T product, GCAR and SCL mRNA LNP technology in 1H25. Studies will assess vector selectivity (tropism), biodistribution, pharmacokinetics, pharmacodynamics and safety as well as the influence of SCL mRNA administration on GCAR cellular PK. Results from these studies will inform regulatory discussions for IND enabling activities in the US for its 1st GCAR product for clinical investigation.

"We are pleased with these data that support our decade-long vision to expand the safety and efficacy of CAR-T into solid tumors," stated Gregory Frost, Ph.D. Chairman and CEO of EXUMA Biotech. "Towards the second and equally important dimension of this vision, we look forward to advancing these and other CARs into clinical investigation with our in vivo GCAR platform, enabled by EXUMA’s novel FITNESS DRIVER and CD3-targeted and synthetic car ligand (SCL) technologies, having the potential to provide a truly off-the-shelf solution for patients."