On April 18, 2023 Palleon Pharmaceuticals, a clinical-stage company pioneering glyco-immunology drug development to treat cancer and inflammatory diseases, reported the initial Phase 1 results from the GLIMMER-01 trial of its lead EAGLE oncology platform program, E-602, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023 in Orlando, Florida (Press release, Palleon Pharmaceuticals, APR 18, 2023, View Source [SID1234630286]).

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The study demonstrated proof of mechanism for E-602, a first-in-class glyco-immune checkpoint inhibitor, including dose dependent desialylation and dose dependent immune system activation. Additionally, E-602 was found to be well tolerated across the entire dose range evaluated with no dose limiting toxicities. Having met pre-specified gating criteria based on safety and pharmacodynamic activity, Palleon announced plans to proceed with Phase 2 evaluation.

"E-602 represents a truly novel immuno-oncology candidate that builds on the promise of glycobiology, a field of study that offers unprecedented opportunities for drug development in cancer and other diseases," said David Feltquate, M.D., Ph.D., Chief Medical Officer of Palleon Pharmaceuticals. "Establishing proof of mechanism for this approach provides the validation necessary to initiate Phase 2 evaluation and take next steps towards our team’s shared goal of offering new options for patients in need."

"It is exciting to see the first clinical results generated from Palleon’s EAGLE glyco-immunology drug development platform," said Carolyn Bertozzi, Ph.D., Palleon Scientific Co-Founder and 2022 Nobel laureate. "Palleon is advancing an entirely new axis of immune modulation, defined by the interaction between sialoglycans and their receptors, which may benefit patients who do not respond to current medications."

In the initial results from the GLIMMER-01 trial presented by lead investigator, Jason Luke, M.D., of UPMC Hillman Cancer Center, 40 patients were treated with at least one dose of E-602, the most common tumors treated being colorectal (n=21) and pancreatic (n=10). Doses up to 30 mg/kg were tolerated with no dose-limiting toxicities. Both dose-dependent desialylation and immune system activation, as measured by increases in activated (CD69+) immune cells in circulation and elevation of circulating cytokines and chemokines including IP-10/CXCL10, were observed. Phase 2 studies will evaluate clinical activity of E-602 monotherapy in patients with lung cancer and melanoma.

The presentation can be found in the Palleon Publications section of the Education Hub page of our website.

On April 18, 2023 Exai Bio reported new data demonstrating that its novel RNA- and AI-based platform detected non-small cell lung cancer with high accuracy, at the earliest stages and for the smallest tumors, in both training and validation cohorts (Press release, Exai Bio, APR 18, 2023, View Source [SID1234630285]). In the independent validation cohort, stage I sensitivity was 96% and tumor size T1a-b sensitivity was 94%, at 90% specificity. These findings continue to highlight the power of Exai’s proprietary technology to detect cancer at its earliest stages from a blood draw. This study will be presented today at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2023 annual meeting.

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"These results demonstrate the unique advantages of our RNA-based liquid biopsy platform in early detection," said Patrick Arensdorf, Chief Executive Officer of Exai. "We set the bar high in this study, emphasizing small and early stage tumors, in order to address head-on the unmet need for earlier lung cancer detection. Exai’s platform reveals actionable insights into novel cancer biology in order to achieve our ultimate goal of improving patient outcomes."

Today’s non-small cell lung cancer results at AACR (Free AACR Whitepaper) expand a growing body of evidence that Exai’s platform can be used across multiple tumor types and clinical applications, using standard blood samples. Previously, Exai has presented breast cancer early detection and screening data at the San Antonio Breast Cancer Symposium (SABCS) 2022, monitoring and molecular residual disease detection data in breast cancer at SABCS 2021, and colorectal cancer early detection and screening data at the 2022 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) meeting.

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 Exai’s proprietary artificial intelligence, this unique platform has several scientific and practical advantages over tests that focus on circulating tumor DNA including sensitivity, specificity and informative properties for active cancer biology. 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

Presentation Title: Blood-based Early Detection of Non Small Cell Lung Cancer Using Orphan Noncoding RNAs

Session Title: Increasing the Clinical Utility of Cell Free DNA Testing

Date: Tuesday, 4/18/23, 2:30 – 4:30 PM EDT

Authors: Mehran Karimzadeh, Jeffrey Wang, Aiden Sababi, Dare Afolabi, Ti Lam, Alice Huang, Diana Corti, Kristle Garcia, Seda Kilinc, Allen Zhao, Jeff J Wang, Taylor Cavazos, Patrick Arensdorf, Kimberly Chau, Helen Li, Hani Goodarzi, Lisa Fish, Fereydoun Hormozdiari, Babak Alipanahi

On April 18, 2023 Juntendo University, Sysmex Corporation, and ThinkCyte K.K. have reported a collaborative research partnership to advance the early detection and treatment of chronic myelogenous leukemia (CML) (Press release, Juntendo University, APR 18, 2023, View Source [SID1234630283]). The joint research program aims to develop a sensitive diagnostic approach for blood cancers and deliver critical new cellular insights to advance the treatment of CML using Ghost Cytometry, ThinkCyte’s artificial intelligence (AI)-driven cell characterization and sorting technology.

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Under the partnership, the research teams will apply a novel approach that captures high-resolution information about the structure, shape, and size of cells (morphology) at high speed. By generating ‘morphometric signatures’ directly from CML patient samples, the research teams seek to identify, isolate, and characterize disease-driving cells. Detecting small numbers of disease-driving tumor cells in CML can aid in the early diagnosis and intervention of disease; a crucial factor affecting long-term outcomes. By isolating these cells, researchers will also be able to advance the development of CML treatments by gaining a better understanding of how patients develop resistance to existing drugs and identifying new approaches to treating the disease.

"Although the development of tyrosine kinase inhibitors (TKIs) has greatly improved the prognosis of patients with CML, the rate of disease relapse after stopping TKI therapy is still very high," said Dr. Tomoiku Takaku MD, Ph.D., Associate Professor of Hematology at Juntendo University. "The development of new rapid and minimally invasive tools to diagnose the disease early and guide our understanding of how therapeutic agents targeting leukemia stem cells is key to advancing patient care. We believe this research will lead to findings that help reduce the burden of high drug costs and unwanted daily side effects that many CML patients face."

The three organizations have been jointly developing approaches to capture unique, disease-specific morphological differences between blood cancer cells and normal white blood cells using Ghost Cytometry.

"Ghost Cytometry has the potential to be a powerful new cell analysis technology for many hematological conditions. Starting with CML, we believe that the diagnosis and treatment of blood cancer be greatly advanced by this joint research program," said Tomokazu Yoshida, Member of the Managing Board and Senior Executive Officer Managing Director, CTO at Sysmex Corporation. "Sysmex has a rich history of expertise in cellular measurement technology cultivated in the diagnostic field and we are proud to contribute our research and development expertise to Juntendo University and ThinkCyte to provide direct impact to CML patients."

The research is supported in part by Japan’s Small and Medium Enterprise Agency’s "Go-Tech Project," which seeks to advance technologies with a demonstrated ability to modernize basic research in future high-growth industries.

"We are very excited about the research partnership with Juntendo University and Sysmex, who were quick to focus on our technology’s potential to advance research in areas of unmet medical need," said Waichiro Katsuda at ThinkCyte. "We believe that Ghost Cytometry can be an innovative approach to developing new diagnostic and therapeutic methods for many indications and look forward to the results of this joint research effort."

On April 18, 2023 Nordic Nanovector ASA (OSE: NANOV) ("Nordic Nanovector" or the "Company") reported that full results from its Phase 2 clinical trials of Betalutin (177 Lu lilotomab satetraxetan) in resistant/refractory (R/R) indolent non-Hodgkin’s lymphoma (NHL) have been published at EudraCT, the European Union Drug Regulating Authorities Clinical Trials Database (the database for all interventional clinical trials on medicinal products submitted to the National Competent Authorities (NCAs) of the European Union) (Press release, Nordic Nanovector, APR 18, 2023, View Source [SID1234630284]). The data from the Phase 1b/2a LYMRIT 37-01 and the Phase 2b PARADIGME studies can be found via this link:

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EU Clinical Trials Register

As previously announced on 5 July 2022, the PARADIGME trial of Betalutin in 3rd-line follicular lymphoma patients refractory to rituximab/anti-CD20 (3L R/R FL) was discontinued following a comprehensive review and independent data evaluation and a subsequent request for regulatory agency interaction. The data from the 109 patients enrolled in PARADIGME up until its discontinuation show:

Overall response rate (ORR) was 38.9% and 32.1%; complete response (CR) rate was 20.8% and 14.3% in participants receiving doses of 40/15 (Betalutin dose of 15 MBq/kg after a pre-dose of 40 mg lilotomab) and 100/20 (Betalutin dose of 20 MBq/kg after a pre-dose of 100 mg lilotomab), respectively.
Median duration of response (DoR) was approximately 8.5 months for the 40/15 dose and 3.4 months for the 100/20 dose. Median duration of complete response (DoCR) was 8.5 months for 40/15 and 9.2 months for 100/20. DoR and DoCR are difficult to interpret due to the small number of responders.
Over half the participants had progressed 6 months following treatment. The median progression-free survival (PFS) was 5.9 months versus 5.8 months with 40/15 and 100/20, respectively.
The majority of treatment emergent adverse events (TEAEs) were due to cytopenias, most notably decreases in platelets (thrombocytopenia was observed in 19 [16.8%] and platelet count decreased in 11 [9.7%] participants) and neutrophils (neutropenia in 18 [15.9%] and decreased neutrophil count in six [5.3%] participants). Anaemia and fatigue were also reported in >10% of participants.
As previously communicated in the 5 July 2022 announcement, the former Board of Directors of Nordic Nanovector took the decision to wind-down PARADIGME in a structured manner while ensuring that patients received the best possible care during this period, as the observed profile did not fully meet the objectives set out for the study. As a result, the former Board was of the opinion that the demonstrated profile was no longer sufficiently competitive to bring Betalutin to the market in 3L R/R FL within a timeframe that made financial and commercial sense for the Company. The current board and management concurs with the decision to discontinue PARADIGME and Betalutin development in the 3L R/R FL indication.

The Company still believes there could be a market for Betalutin in light of its safety profile, promising efficacy in earlier lines of therapy and unique feature of being delivered as a one-time dose. However, a potential new development programme would need to be conducted in a different patient population and line of treatment and would require significant financial resources.

The Company is exploring all strategic options including potential partnerships to see if there is a possible way forward for Betalutin in an alternative setting.

Pipeline update:

The rest of Nordic Nanovector’s pipeline consists of:

1. Humalutin: a radioimmunotherapy candidate based on a chimeric anti-CD37 antibody and the beta-emitting radionuclide lutetium-177 for NHL. The project has been on hold since 2016 and all preclinical data have been published in the following journals:

· The European Journal of Nuclear Medicine and Molecular Imaging
· Nature Scientific Reports
· PLOS ONE
2. Alpha37: an alpha-emitting radioimmunotherapy candidate based on a chimeric anti-CD37 antibody conjugated to lead-212. The project is a collaboration with partner OranoMed and has been on hold since 2021. All preclinical data has been published in:

PLOS ONE
3. Fully humanized anti-CD37 antibodies with potential in haematological cancers and autoimmune diseases. Preclinical data were presented in two posters at ASH (Free ASH Whitepaper), both available on the Nordic Nanovector website:

ASH posters
The project has been on hold in 2023.

4. CD37 DOTA CAR-T cell opportunity in haematological cancers is a research collaboration with the University of Pennsylvania. Data from preliminary investigations were inconclusive and the project has been put on hold.

5. Solid tumour radioimmunotherapy: a project directed at radioimmunotherapy for solid tumours, where target identification has been concluded and several interesting molecular targets for solid tumour indications have been identified. Validation of targets and testing of minimal viable products are being evaluated.

The Board continues to focus on reducing costs where necessary to enable the Company to minimise cash burn until a strategic partner can be found.

No assurances can be given as to the outcome or timing of the ongoing strategic review process. The Company will put forward any recommended proposals for resolution by shareholders in due course.

On April 18, 2023 OnQuality Pharmaceuticals ("OnQuality"), a targeted oncology supportive therapy company developing innovative medications to address unmet needs in oncodermatology and oncogastroenterology (cancer therapy-induced toxicities occurring in the skin and gastrointestinal tract) and to improve the quality of life for patients receiving anticancer medications, reported that it has presented preclinical data on OQL025 and OQL06x, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting (Press release, OnQuality Pharmaceuticals, APR 18, 2023, View Source [SID1234630282]). The conference is being held in Orlando, FL, April 14-19, 2023.

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EGFR inhibitors are commonly used for the treatment of various cancers, including lung and colorectal cancers. However, dose-limiting skin toxicities and diarrhea are frequently associated with the use of this class of anticancer therapies. Management of these toxicities includes specific guidance for dosage adjustment/therapy interruption to realize the benefit of EGFR inhibitor treatment and to minimize negative effects on patient’s quality of life.

EGFR inhibitor-induced acneiform rash frequently appears on the face, neck, upper chest and back with an incidence of 20% to over 90%. The incidence of EGFR inhibitor-induced diarrhea can be as high as 90%. Moderate or severe diarrhea can lead to dehydration, electrolyte imbalances, infection, and other serious complications. Patients experiencing diarrhea have a 40% higher rate of cancer therapy discontinuation.

OnQuality is developing OQL025, a Janus Kinase (JAK) inhibitor administered as a topical cream, and OQL06x, an oral gut-restricted JAK inhibitor. Topical OQL025 delayed the onset and the severity of EGFR inhibitor-induced rash with low systemic exposure in preclinical models. In murine models of diarrhea caused by afatanib, orally administered OQL06x reduced the severity of EGFR inhibitor-induced diarrhea when compared to placebo. The improvement was accomplished with minimal systemic exposure, as OQL06x has been designed to have gut-restrictive properties, reducing the potential to cause systemic toxicities and interference with EGFR inhibitor anti-cancer efficacy.

At AACR (Free AACR Whitepaper), OnQuality presented:
Title: OQL025, a topical cream for the prevention of epidermal growth factor receptor inhibitor-induced skin rash
Presenter: Robert C. Tyler, Ph.D.
Session Category: Clinical Research Excluding Trials
Session Title: Cancer Outcomes 1
Session Date and Time: Monday Apr 17, 2023 1:30 PM – 5:00 PM
Abstract Number: 3211

Title: OQL06x, a gut-restricted janus kinase inhibitor to control epidermal growth factor receptor inhibitor-induced diarrhea
Presenter: Robert C. Tyler, Ph.D.
Session Category: Clinical Research Excluding Trials
Session Title: Cancer Outcomes 1
Session Date and Time: Monday Apr 17, 2023 1:30 PM – 5:00 PM
Abstract Number: 3212

"OnQuality is committed to developing OQL025 and OQL06x for the prevention of EGFR inhibitor-induced acneiform rash and diarrhea, improving quality of life and potentially treatment outcomes for cancer patients. Our preclinical data demonstrated our novel approaches of OQL025 and OQL06x reduced specific EGFR inhibitor-induced toxicities while minimizing the potential to interfere with systemically administered anti-cancer regimens," said Robert C. Tyler, Ph.D., Senior Medical Director of OnQuality. "It was exciting to share these data and engage in meaningful scientific discussions about the unmet need for EGFR inhibitor-induced acneiform rash and diarrhea at the conference."

Details regarding the poster presentations can be found on the AACR (Free AACR Whitepaper) website.