On April 8, 2024 PanTher Therapeutics ("PanTher" or the "Company"), a clinical-stage oncology company developing high-dose, long lasting, localized treatments for cancer, reported positive data from a first-in-human study of PTM-101, a highly potent chemotherapeutic agent (paclitaxel) combined with an absorbable polymer formulated as a flexible film, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, taking place April 5-10th in San Diego (Press release, PanTher Therapeutics, APR 8, 2024, View Source [SID1234641909]).

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This first-in-human study enrolled three patients at a single center in Australia to assess the safety and surgical feasibility of a single, low-dose treatment of PTM-101. PTM-101 was placed directly onto the pancreas, overlying the location of the tumor using standard laparoscopic equipment as part of a disease staging assessment. Once in place over the tumor site, PTM-101 locally delivered a sustained dose of the chemotherapeutic agent over four weeks. Approximately three weeks after placement of PTM-101, all participants began standard of care therapy, which included treatment with mFOLFIRINOX.

Results of the clinical trial demonstrated that PTM-101 reduced the size of pancreatic tumors in all three patients. During the 24 weeks of the prospective phase of the study, the reduction in tumor thickness beneath PTM-101 ranged from 16% to 26%. Two patients had a significant reduction in overall tumor volume (40% and 70%). PTM-101 was also shown to have a favorable safety profile, as it was well-tolerated with no peritonitis, pancreatitis, infection, or hematological toxicity. The chemotherapeutic agent remained localized to the pancreas in all patients, with no detection of systemic paclitaxel at any timepoint.

"Historically, there have been significant clinical challenges realizing the benefits of chemotherapeutics when they are administered systemically. Maintaining a high drug concentration is limited by the route of administration as well as toxicity, which negatively impacts the effectiveness of the drug," said Laura Indolfi, PhD, Chief Executive Officer, and co-founder of PanTher Therapeutics. "We are encouraged by the early clinical data of PTM-101 in patients with locally advanced pancreatic cancer, further validating the potential of our Sagittari platform to deliver high-concentrations of drug directly to the site of a tumor for an extended period of time, without commonly observed undesired side effects."

"Use of PTM-101 to locally administer a highly potent drug, without the limitations from systemic safety and tolerability issues, offers the potential to facilitate significant improvement in patient outcomes, which is clearly needed in the treatment of pancreatic cancer," said Charles Pilgrim, MD, PhD, Associate Professor of Surgery at the Alfred Central Clinical School at Monash University, and principal investigator of the PTM-101 phase 1 clinical trial. "The ability of PTM-101, in combination with standard of care chemotherapy, to shrink pancreatic tumors as observed in this initial study is promising. The prognosis for patients with pancreatic cancer can be particularly devastating, as it is often detected at an advanced stage, at which point there are limited treatment options. Given the trajectory for this cancer, I am very encouraged by the results from the clinical trial of PTM-101 in locally advanced cases and the ease of integrating the treatment into current clinical practice and standard laparoscopic procedures."

PanTher presented a second poster at AACR (Free AACR Whitepaper) describing the non-clinical development of PTM-101.

Both posters are available on the PanTher Therapeutics website.

On April 8, 2024 Exai Bio reported new breast cancer data at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2024 annual meeting. In a new study, Exai’s novel RNA- and AI-based liquid biopsy platform demonstrated stage I breast cancer detection sensitivity of 90% and ductal carcinoma in situ (DCIS) sensitivity of 88%, both at 90% specificity (Press release, Exai Bio, APR 8, 2024, View Source [SID1234641908]). In addition, the study showed the platform’s unique capability to distinguish low grade, less aggressive DCIS from invasive breast cancer with 87% sensitivity, at 90% specificity using a standard blood sample. More than 55,000 women were diagnosed with DCIS in 2023 in the United States. The current standard of care treatment for the majority of these women is invasive treatment despite the fact that an estimated 60–80% of cases do not progress to cancer. These early data suggest a blood test can become an effective way to not only detect early-stage breast cancer but also monitor low grade DCIS so that more women can have the option of avoiding aggressive or unnecessary treatment.

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"These results further validate the power of Exai’s novel RNA- and AI-based liquid biopsy platform to detect breast cancer at its earliest stages with high sensitivity, overcoming the limitations of DNA-based approaches"

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"These results further validate the power of Exai’s novel RNA- and AI-based liquid biopsy platform to detect breast cancer at its earliest stages with high sensitivity, overcoming the limitations of DNA-based approaches," stated Pat Arensdorf, Chief Executive Officer of Exai Bio. "In addition to strong early detection performance, this study also demonstrated for the first time that our platform can distinguish low grade DCIS from invasive breast cancer with high accuracy. These findings are very promising and indicate the potential for a blood-based test to monitor women who are diagnosed with low grade DCIS."

In addition, Exai announced results from a new breast cancer molecular residual disease (MRD) study conducted in collaboration with the University of Kansas Medical Center. The study demonstrated that Exai’s tumor-naive platform — which does not require sequencing the tumor tissue — can accurately predict survival in the post-adjuvant setting for patients with triple negative breast cancer. These results suggest the potential for Exai’s platform to aid in tailoring adjuvant treatment for individual triple negative breast cancer patients.

Exai’s platform uses RNA sequencing to identify a novel category of cancer-associated, small non-coding RNAs, termed orphan non-coding RNAs (oncRNAs). oncRNAs are actively secreted from living cancer cells and are stable and abundant in the blood of cancer patients. Exai has created a catalog of hundreds of thousands of oncRNAs and thousands of patient oncRNA profiles, spanning all major cancer types. When combined with proprietary artificial intelligence technology, the Exai platform has multiple technical and operational advantages over tests that utilize circulating tumor DNA. These include superior sensitivity and specificity, as well as the ability to reveal dynamic changes in the biology of a patient’s tumor over time. Exai’s universal platform can be used across multiple cancer care settings such as screening and early detection, monitoring, molecular residual disease, and therapy selection.

AACR Presentation Details

Title: Beyond detection: AI-based classification of breast cancer invasiveness using cell-free orphan non-coding RNAs

Abstract Number: 3678

Session: Clinical Research Excluding Trial, Circulating Nucleic Acids 3, Poster Section 41

Authors: M. Karimzadeh, T. Cavazos, N. Chen, N. Tbeileh, D. Siegel, A. Momen-Roknabadi, J. Yen, J. Ku, S. Chen, D. Corti, A. Huang, D. Nguyen, R. Hanna, T. Lam, S. Kilinc, P. Murzynowski, J. Wang, X. Zhao, A. Pohl, B. Behsaz, H. Li, L. Fish, K. Chau, L. Van’t Veer, L. Esserman, P. Arensdorf, H. Goodarzi, F. Hormozdiari, B. Alipanahi

Title: Orphan non-coding RNA (oncRNA) liquid biopsy assay is prognostic for survival in patients with triple-negative breast cancer (TNBC) and residual disease

Abstract Number: 5215

Session: Clinical Research Excluding Trial, Prognostic Biomarkers 1, Poster Section 46

Authors: R. Yoder, J. Yen, M. Karimzadeh, J. Staley, I. Fernandez, A. Heinrich, F. Hormozdiari, J. Gregg, A. Godwin, I. Acerbi, R. Trivedi, B. Alipanahi, S. Stecklein, P. Sharma

On April 8, 2024 Tubulis reported comprehensive preclinical data on its two lead antibody-drug conjugate (ADC) candidates TUB-030 and TUB-040 at this year’s Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) in San Diego (Press release, Tubulis, APR 8, 2024, View Source [SID1234641907]). The poster presentations contained preclinical data, highlighting the ability of the two next-generation Tubutecan ADCs to create effective and durable responses even in low target-expressing tumor mouse models. Tubulis is leveraging a proprietary suite of platform technologies to build a pipeline of uniquely matched ADC candidates that combine the right targeting molecule, conjugation chemistry and payload to deliver the true therapeutic value of the ADC approach. The company’s lead candidates, both targeting solid tumor indications, are in late-stage preclinical testing, with TUB-040 ready for clinical evaluation.

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"These compelling preclinical data sets for both of our lead ADC candidates, TUB-030 and TUB-040, support how our proprietary platforms create ADCs with unique biophysical properties allowing for continued and durable on-tumor delivery of the payload. The in vivo studies have demonstrated that both candidates show strong, long-lasting anti-tumor activity, even at lower expression levels of the respective targets," said Jonas Helma-Smets, Chief Scientific Officer of Tubulis. "Our ADCs are highly differentiated compared to other ADCs on the market and we look forward to translating these findings into the clinic with the goal of improving overall survival and duration of response in patients across a broad range of solid tumors. Starting with TUB-040, we aim to initiate first clinical trials this year and thereby provide clinical proof-of-concept for our next-generation ADCs and our differentiated platform approach to ADC design."

Both ADC candidates are comprised of a humanized, target-specific, Fc-silenced IgG1 antibody conjugated to the topoisomerase-1 inhibitor Exatecan with Tubulis’ Tubutecan linker-payload platform via the proprietary P5 conjugation platform, resulting in highly stable and homogenous drug-to-antibody-ratio of 8 (DAR8) ADCs. Compared to maleimide-conjugated ADCs, TUB-030 and TUB-040 both showed superior stability and minimal loss of linker-payload conjugation.

Highlights of Tubulis’ preclinical data presented at AACR (Free AACR Whitepaper) 2024:

TUB-040

TUB-040 is built with novel Tubutecan linker-payload chemistry and superb biophysical properties, targeting Napi2b, a highly overexpressed antigen in ovarian cancer and lung adenocarcinoma
The ADC candidate is highly stable and highly inert in circulation, enabling powerful and continued on-tumor delivery of the payload, leading to complete eradication of tumors with a low dose single treatment in multiple ovarian cancer mouse models
Enabled by the differentiated Tubutecan linker-payload and strong bystander activity, TUB-040 showed significantly better durability of antitumor activity in preclinical models compared to lifastuzumab vedotin
In ovarian cancer and non-small-cell lung cancer (NSCLC) patient derived xenograft mouse models, treatment with TUB-040 led to robust long-lasting tumor regressions
Repeat-dose toxicology studies of TUB-040 in non-human primates demonstrated that TUB-040 was well tolerated with minor and reversible adverse effects
TUB-030

TUB-030 is built with novel Tubutecan linker-payload chemistry and superb biophysical properties, targeting 5T4, a tumor-associated antigen expressed in a broad range of solid tumors
The ADC candidate demonstrated target-specific cytotoxicity as well as strong bystander activity, facilitating the destruction of cells that do not express the target antigen but are in the direct vicinity of the targeted tumor cell, thereby broadening the effect of the ADC
A single treatment with TUB-030 was shown to eliminate tumors in a triple negative breast cancer mouse model, whereas PF06263507, a clinically tested comparator ADC led to re-growth of tumors.
In over 25 patient derived xenograft mouse models of various types of cancer, TUB-030 showed high efficacy rates even at low 5T4 expression levels and achieved long-lasting and durable anti-tumor activity
TUB-030 was well tolerated in non-human primates and showed highly restricted binding to normal fresh frozen human tissues
The full abstracts were published in an online-only proceedings supplement to the AACR (Free AACR Whitepaper) journal, Cancer Research in March and can be accessed here.

On April 8, 2024 Photocure ASA (OSE: PHO), the Bladder Cancer Company, reported its participation in the congress, and two abstract presentations at the 2024 European Association of Urology congress (EAU) in Paris, France, highlighting the benefits of Blue Light Cystoscopy (BLC) in Bladder Cancer management (Press release, PhotoCure, APR 8, 2024, View Source [SID1234641906]).

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The EAU annual meeting is one of the largest international meetings in the urology calendar, showcasing the latest and most relevant clinical and scientific advancements in this area of patient care. This year’s event was held on April 5-8, 2024, and attracted urologists from all over the world. Similar to last year, Photocure will make 2024 EAU bladder cancer session highlights available to healthcare professionals post event, by means of video interviews with the presenters of these sessions on the Photocure booth D26. This highly engaging and successful initiative is once again supported by two of the leading names in Bladder Cancer in Europe, Prof. M. Rouprêt, APHP, Sorbonne University Paris, France and Prof. P. Gontero, Division of Urology, University of Studies of Torino, Italy.

In addition to this educational activity, the EAU scientific program prominently features Photocure’s Hexvix product and/or the blue light cystoscopy procedure in which it is used. In particular, two notable abstract presentations were:

Outpatient laser coagulation of low-grade intermediate risk bladder tumor compared with TUR-BT, 12 months and long-term follow-up of a non-inferiority RCT (Abstract session 36 NMIBC: Benefits and harms of various treatment options, Sunday, 7 April, 17:15-18:45)

Treatment of recurrent low grade intermediate risk bladder tumor is burdensome for patients and health care system. The primary objective of this study was to evaluate 12 months recurrence-free survival after out-patient department photo coagulation of bladder tumors (PC-BT) is non-inferior to PDD-assisted TUR-BT in patients with recurrent Ta low grade bladder tumor. 154 patients were randomized for PC-BT and 146 for TUR-BT. 12 months follow-up data were available for 299 patients. 12 months recurrence-free survival was 42.2% after PC-BT and 44.1% after TUR-BT, the difference 1.9% (95%CI -9.3 to 13.2) in favor of TUR-BT. Regarding 12 months recurrence-free survival, the noninferiority criterion was met. Recurrence-free survival after OPD PC-BT is noninferior to TUR-BT at 12 months follow-up. Incidence of long-term stage progression after PC-BT is noninferior to TUR-BT and very low after both treatment modalities. Treatment of recurrent Ta low grade intermediate risk bladder tumors in out-patient department with PC-BT appears to be a safe alternative to TUR-BT.

Read the abstract: View Source

A prospective, comparative, within-patient controlled multicenter phase III study comparing blue light cystoscopy versus white light cystoscopy for the detection of bladder cancer using modern HD 4K equipment (Abstract session 46, Monday, 8 April, 12:30-14:00)

The study enrolled a total of 158 patients in a randomized controlled trial, and 114 patients underwent Hexvix blue light cystoscopy (BLC) and were in the full analysis set. Among patients diagnosed with Ta, T1, or CIS, 42 out of 97 patients (43.3%) had at least one lesion detected by BLC but not by white light cystoscopy (WLC) (p<0.0001). Thirteen patients had CIS of which 11 (84.6%) showed additional CIS lesions. The BLC detection rates for PUNLMP, CIS, Ta, T1, and T2 ~ T4 tumors were NA, 94.7%, 100%, 98.2%, and 100%, respectively, while the WLC detection rates were NA, 42.1%, 76.1%, 91.2%, and 100%. This study confirms the superiority of HAL BLC over WLC in the detection of bladder cancer even if improved WLC using HD 4K equipment is utilized. In particular, additional high-risk difficult to see CIS lesions have been identified in 85% of all CIS patients only by HAL BLC. The quality of resection is still a key cornerstone in the treatment of NMIBC of which BLC remains a crucial part despite the further development of WLC imaging.

Read the abstract: View Source

"With the rapid advancement of technologies, emerging trends towards precision medicine and introduction of novel targeted agents which are transforming bladder cancer care, there is a renewed emphasis on the importance of the diagnostic process. Getting a correct and timely diagnosis is more important than ever. It’s key to optimizing the subsequent care pathways and treatment decisions," said Anders Neijber, Chief Medical Officer of Photocure. "These new results presented at EAU continue to emphasize the importance of using Blue Light Cystoscopy in the diagnosis of bladder cancer. BLC has been shown to clinically increase TURBT quality, more accurately stage disease, and enable better recurrence monitoring, supporting the long-term utility to help improve the lives of patients with bladder cancer."

"Every year we see new data added to the body of evidence on Hexvix/blue light cystoscopy benefits, including with high-definition equipment. In Europe, our teams focus on helping their customers achieve the best possible image quality for BLC. We are convinced that when it comes to bladder tumor detection methods "seeing is believing", which is also our booth theme for this year’s EAU. Many urologists try BLC, see what they see, and never look back", added Susanne Strauss, Vice President and General Manager Europe.

*TUR-BT/TURBT: trans-urethral resection of bladder tumors

Note to editors:

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About Bladder Cancer

Bladder cancer ranks as the 8th most common cancer worldwide – the 5th most common in men – with 1 949 000 prevalent cases (5-year prevalence rate)1a, 614 000 new cases and more than 220 000 deaths in 2022.1b
Approx. 75% of all bladder cancer cases occur in men.1 It has a high recurrence rate with up to 61% in year one and up to 78% over five years.2 Bladder cancer has the highest lifetime treatment costs per patient of all cancers.3
Bladder cancer is a costly, potentially progressive disease for which patients have to undergo multiple cystoscopies due to the high risk of recurrence. There is an urgent need to improve both the diagnosis and the management of bladder cancer for the benefit of patients and healthcare systems alike.
Bladder cancer is classified into two types, non-muscle invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC), depending on the depth of invasion in the bladder wall. NMIBC remains in the inner layer of cells lining the bladder. These cancers are the most common (75%) of all BC cases and include the subtypes Ta, carcinoma in situ (CIS) and T1 lesions. In MIBC the cancer has grown into deeper layers of the bladder wall. These cancers, including subtypes T2, T3 and T4, are more likely to spread and are harder to treat.4

1 Globocan. a) 5-year prevalence / b) incidence/mortality by population. Available at: View Source, accessed [February 2024].
2 Babjuk M, et al. Eur Urol. 2019; 76(5): 639-657
3 Sievert KD et al. World J Urol 2009;27:295–300
4 Bladder Cancer. American Cancer Society. View Source

About Hexvix/Cysview (hexaminolevulinate HCl)

Hexvix/Cysview is a drug that preferentially accumulates in cancer cells in the bladder, making them glow bright pink during Blue Light Cystoscopy (BLC). BLC with Hexvix/Cysview, compared to standard white light cystoscopy alone, improves the detection of tumors and leads to more complete resection, fewer residual tumors, and better management decisions.
Cysview is the tradename in the U.S. and Canada, Hexvix is the tradename in all other markets. Photocure is commercializing Cysview/Hexvix directly in the U.S. and Europe and has strategic partnerships for the commercialization of Hexvix/Cysview in China, Chile, Australia, New Zealand and Israel. Please refer to View Source for further information on our commercial partners.

On April 8, 2024 Verismo Therapeutics, a clinical-stage CAR T company developing the novel KIR-CAR platform technology, reported that an abstract has been accepted for poster presentation at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2024 (AACR 2024), to be held in San Diego on April 5-10, 2024 (Press release, Verismo Therapeutics, APR 8, 2024, View Source [SID1234641905]).

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Presentation Details

Title: Evaluating the relationship of affinity, functional avidity, and in vivo potency in KIR-CAR T cells
Abstract Number: 6332
Date and Time: Tuesday, April 9th: 1:30 – 5:00 p.m.
Presenting Author: Jun Xu, PhD
Description: We have previously shown that a novel killer immunoglobulin receptor (KIR)-based CAR expressed in T cells as a multichain receptor with DAP12 (KIR-CAR T) has enhanced anti-tumor activity compared to conventional second-generation CAR T cells in several preclinical solid tumor models suggesting that this platform may show better activity in aggressive lymphoma. In this study, we aimed to evaluate the relationship of affinity, functional avidity, and in vivo potency of novel CD19 binders in a KIR-based CAR T cell. This study paves the way for developing an improved CD19-specific KIR-CAR T cell therapy for treating pts with B-cell malignancies.

About the KIR-CAR Platform
The KIR-CAR platform is a multi-chain CAR T cell therapy and has been shown in preclinical animal models to be capable of maintaining antitumor T cell activity even in challenging tumor microenvironments. Using NK cell derived KIR and DAP12 split signaling provides a novel combined activation and co-stimulation separate from the usual T cell stimulation pathways. It also enables sustained chimeric receptor expression and improves KIR-CAR T cell long term function. This results in prolonged T cell functional persistence and leads to regression of solid tumors in preclinical models that are resistant to traditional CAR T cell therapies. The KIR-CAR platform is being investigated in combination with many additional emerging technologies to potentially provide the next-generation multimodal targeted immunotherapy for patients in need.