On April 4, 2024 Ariceum Therapeutics (Ariceum), a private biotech company developing radiopharmaceutical products for the diagnosis and treatment of certain hard-to-treat cancers, reported that it will be presenting a poster, demonstrating its new findings on the discovery of novel macrocyclic peptide radioligands for tumor therapy by mRNA display in collaboration with research partner, UCB, a global pharmaceutical company, at this year’s American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, held 5-10 April 2024 in San Diego, California (Press release, Ariceum Therapeutics, APR 4, 2024, View Source [SID1234641772]).

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The findings describe the selection and initial characterization of macrocyclic peptides against an undisclosed target discovered using UCB’s mRNA-display technology platform, ExtremeDiversity. Macrocyclic peptides are potent ligands for radioligand therapeutics (RLT) that aim to selectively deliver radioisotopes to cancer tissues to eradicate tumor cells while limiting the damage to surrounding tissues. This new data highlights the potential of UCB’s mRNA display platform for fast and efficient discovery of highly specific macrocyclic peptides with optimal binding properties suitable for RLT.

Manfred Rüdiger, Chief Executive Officer at Ariceum Therapeutics, said: "Following our exclusive, strategic research collaboration with UCB, we look forward to presenting new findings related to the identification of highly specific macrocyclic peptides for use in radioligand therapeutics at this year’s AACR (Free AACR Whitepaper) Annual Meeting. These data have positive implications for the future development of RLT and are a potential game-changer in precision cancer therapy. AACR (Free AACR Whitepaper)’s Annual Meeting is the perfect industry forum at the forefront of cancer research at which to present our findings."

Details of the poster presentation are as follow:

Title: Discovery of novel macrocyclic peptide radioligands for tumor therapy by mRNA display
Presenting Author: Anika Jaekel, Senior Director, Head of Translational Biology and Non-Clinical Pharmacology at Ariceum Therapeutics
Session Category: Experimental and Molecular Therapeutics
Session Title: Radiation, Theranostics, Radiotheranostics, Normal Tissue, and Cellular Stress
Session Date and Time: Tuesday 9 April 2024, 1:30 PM – 5:00 PM PDT
Location: Poster Section 29
Poster Board Number: 7
Abstract Number: 6025

Abstracts are available in an online itinerary planner here and will be available in on online only supplement to the AACR (Free AACR Whitepaper) journal Cancer Research one month after the conference.

On April 4, 2024 Adcendo ApS ("Adcendo"), a biotech company focused on the development of first-in-class antibody-drug conjugates (ADCs) for the treatment of cancers with a high unmet medical need, reported that it will be presenting novel data on the expression of its novel ADC target uPARAP and the in vitro and in vivo activity of a uPARAP targeting ADC in glioblastoma multiforme (GBM) at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, held in San Diego, California, from April 5th to April 10th, 2024 (Press release, ADCendo, APR 4, 2024, View Source [SID1234641771]). The data has been evaluated in collaboration with the Finsen Laboratory, Rigshospitalet/BRIC, University of Copenhagen, Copenhagen, Denmark.

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uPARAP is a novel ADC target overexpressed by mesenchymal cancer cells including soft tissue and bone sarcomas, GIST as well as mesothelioma and glioblastoma, and has the potential to play a key role in modulating the tumor microenvironment.

The data demonstrate that uPARAP is strongly over-expressed in glioblastoma cells and that a uPARAP targeting ADC exhibits strong in vivo anti-tumor activity in a glioblastoma PDX model. Based on its differentiated expression profile and rapid internalization capabilities, uPARAP is an attractive novel target for the development of a uPARAP-targeting ADC in this hard-to-treat disease area with a high unmet medical need due to limited treatment options.

Details of the poster presented presentation are as follow:

Presentation title: 6355/16 – Urokinase plasminogen activator receptor-associated protein (uPARAP) is overexpressed in human glioblastomas and is a novel attractive target for antibody-drug conjugates (ADC)

Track: Clinical Research/Immunology

Session: Antibodies 2

Authors: I. Gregersen1, C. R. Løkke1, J. B. Lange1, P. Barkholt1, C. Côme1, T. Broberg1, O. D. Lærum2, M. M. Petersen1, M. Knuuttila3, S.-M. Käkönen3, C. M. Lynch1, D. Mumberg1, N. Behrendt2, L. H. Engelholm 1,2

Date & Time: April 9th, 1.30pm – 5.00pm PDT

Abstracts are available in an online itinerary planner found here, and will be available in an online only supplement to the AACR (Free AACR Whitepaper) journal Cancer Research one month after the conference.

Dominik Mumberg, Chief Scientific Officer at Adcendo, said: "We are excited to share promising data on the expression of uPARAP in glioblastoma as well as encouraging in vivo activity of a uPARAP targeting ADC. In addition to its highly differentiated expression profile in multiple mesenchymal cancers, uPARAP is a constitutively recycling endocytic receptor with unique internalization properties, making it a very attractive ADC target for the benefit of patients."Lars Engelholm, Associate Professor, and group leader at the Cancer Invasion Section of the Finsen Laboratory, said: "Treatment progress and therapeutic options in glioblastoma have so far been very limited. We are extremely encouraged by the data highlighted in this study, which provides further evidence on the potential effectiveness of uPARAP as a novel target for ADCs in glioblastoma multiforme. We look forward to continuing our scientific collaboration with Adcendo to further deepen our insights into the biology of uPARAP and its utility as target for ADC development in multiple mesenchymal cancers."

On April 3, 2024 TransCode Therapeutics, Inc. (NASDAQ: RNAZ), the RNA oncology company committed to more effectively treating cancer using RNA therapeutics, reported financial results for 2023 and recent business progress (Press release, TransCode Therapeutics, APR 3, 2024, View Source [SID1234641817]).

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"We believe 2023 was extremely productive and pivotal for TransCode. We are proud to have advanced our lead therapeutic candidate, TTX-MC138, into the clinic as a first-in-class drug candidate against metastatic cancer. The year was highlighted by preliminary clinical results from our Phase 0 clinical trial with radiolabeled TTX-MC138," said Tom Fitzgerald, interim CEO and CFO of TransCode. "Further, despite very challenging financial markets, we raised over $25 million in equity financings, streamlined our operations for higher efficiency, and signed two strategic collaborations aimed at demonstrating the value of our TTX platform in additional applications. We also continued to achieve other important milestones, with the ultimate objective of fulfilling the promise of RNA therapeutics for oncology applications. We now look forward to our Phase 1 clinical trial of TTX-MC138 which, subject to FDA authorization, is planned to begin in mid-2024."

Key Highlights (2023 and Q1 2024)

· IRB approval for FDA-cleared first-in-human Phase 0 clinical trial with TTX-MC138.
· First patient dosed and preliminary clinical results with radiolabeled TTX-MC138 in the Phase 0 clinical trial.
· Signed a co-research agreement with Debiopharm to develop nucleic acid therapeutics for cancer treatment.
· Signed a joint research and development agreement with Akribion Genomics to develop a CRISPR-derived technology platform for cancer treatment.
· Raised over $25 million in equity financings in an extremely challenging financial environment.
· Refocused our development strategy, prioritizing advancing TTX-MC138 into a Phase 1 clinical trial and reducing cash burn.
· Appointed CFO Tom Fitzgerald as interim CEO and director Philippe Calais as Executive Chairman following the resignation of Michael Dudley as CEO.
· Appointed Daniel Vlock, M.D., as Chief Medical Officer (part-time).
· Regained compliance with Nasdaq’s stockholders’ equity requirement.
· Presented TransCode technology at leading cancer conferences including San Antonio Breast Cancer Symposium, AACR (Free AACR Whitepaper), OTS, and TIDES Europe.

TTX-MC138

· Reported preliminary clinical results suggesting delivery of TTX-MC138 to metastatic lesions in a patient with breast cancer metastatic to lungs, bone, and liver.
· Reported positive preclinical results in a model of glioblastoma showing successful delivery and pharmacodynamic activity in brain tumors.
· Reported positive preclinical results in a model of metastatic pancreatic adenocarcinoma showing 50% inhibition of metastatic progression compared to standard-of-care chemotherapy.
· Received second Orphan Drug Designation from FDA, for TTX-MC138 in pancreatic cancer.

TTX-siPDL1

· Reported positive preclinical results in pancreatic cancer, showing extended survival relative to standard-of-care chemotherapy.

TTX-RIGA

· Reported successful completion of animal studies in a model of melanoma showing arrest of secondary tumor progression.

2024 Corporate and R&D Objectives

With what we expect will be a very exciting year ahead, our 2024 corporate goals, none of which are assured, are to strengthen our organization while raising sufficient capital to continue to advance our research. We will also seek to expand collaborations with strategic partners to further enhance the value of our pipeline.

2024 will also be a critical year for the clinical development of TTX-MC138 and our preclinical portfolio, as we seek to:

· Initiate a Phase 1 clinical trial with TTX-MC138 in patients with advanced solid tumors as soon as we obtain FDA authorization and relevant institutional review board approvals from investigational sites.
· Report preliminary results from the planned Phase 1 trial later this year.
· Publish preclinical results in the second half of the year supporting TTX-MC138 in glioblastoma and pancreatic cancer, TTX-siPDL1 in pancreatic cancer, and TTX-RIGA in melanoma.
· Continue preclinical studies for therapeutic candidates TTX-mRNA and TTX-CRISPR.
· Advance existing strategic partnerships and sign others around TransCode’s TTX delivery platform, TTX-CRISPR, TTX-siRNA, TTX-MC138, and TTX-mRNA candidates.
· Further develop an exploratory test for miRNA-10b.
· If capital resources permit, initiate CMC development to support future IND-enabling studies with TTX-siPDL1 or TTX-RIGA candidates.

2023 Financial Highlights (amounts are approximate)

· Cash was $2.8 million on December 31, 2023, compared to $4.97 million on December 31, 2022.
· Research and development expenses were $12.3 million in 2023 compared to $10.2 million in 2022.
· General and administrative expenses were $7.2 million in 2023 compared to $8.4 million in 2022.
· Operating loss was $19.4 million in 2023 compared to $18.6 million in 2022.

Financial Guidance

TransCode expects that its cash of approximately $2.8 million as of December 31, 2023, together with approximately $6.2 million in net proceeds received from the sale of common stock and warrants in a January 2024 registered direct offering, will be sufficient to fund planned operations into late third quarter or early fourth quarter of 2024.

On April 4, 2024 Novartis reported updated overall survival (OS) results from a pre-planned analysis at approximately 75% information fraction demonstrates an OS hazard ratio less than 1.0 (HR<1.0) in the intent-to-treat (ITT) population unadjusted for cross-over (Press release, Novartis, APR 3, 2024, View Source [SID1234641784]).

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Radiographic progression free survival (rPFS) and other secondary efficacy endpoints are consistent with previous interim analysis results presented in 2023.

With an additional 8 months of follow-up, Pluvicto safety profile remains consistent with previous interim analyses presented in 2023.

Full results will be presented at an upcoming medical congress.

Novartis confirms plans to file in H2 2024.

On April 3, 2024 Conformation-X Therapeutics, LLC, an immune-oncology focused drug development company, reported that it has closed an oversubscribed funding tranche of $3.65M, bringing the total raised since inception to over $13.5M (Press release, Conformation-X Therapeutics, APR 3, 2024, View Source [SID1234641761]). The company unveiled its lead assets by disclosing successful ex vivo and in vivo proof-of-concept studies for its HHLA2 and IL18BP programs, marking critical milestones in the cancer drug development process.

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Drawing inspiration from the fundamental role of protein conformations in disease biology and drug efficacy, Conformation-X applies unparalleled precision to developing novel immune checkpoint inhibitors. The company is creating a comprehensive portfolio of differentiated therapeutics addressing cancer mechanisms that have eluded existing treatments.

"The limitations of current checkpoint therapies are evident, as they don’t fully target the diverse spectrum of mechanisms associated with non-responsiveness and treatment resistance," said Dr. Ali H. Munawar, CEO of Conformation-X Therapeutics.

Despite the pivotal role of PD-1/PD-L1 inhibitors in cancer immunotherapy, several peer-reviewed clinical studies have shown that the overall response rate across various cancers remains at or below 20%. Patients facing resistance to conventional checkpoint therapies encounter a range of challenges. This includes tumors that inherently possess low immunogenicity, are less likely to trigger an immune response, and immune exclusion, which restricts immune cells from the tumor microenvironment (TME). Moreover, complex genetic landscapes featuring oncogenic drivers and epigenetic modifications further contribute to immune evasion and influence treatment outcomes.

Dr. Munawar added, "We are committed to pioneering alternative therapeutic options for these patients by targeting novel biology and molecular pathways. The successive rounds of funding are a testament to our investors’ confidence in the innovation and rigor behind our efforts."

The recent capital infusion accelerates the company towards translational studies of its lead asset and facilitates the expansion of its pipeline. The company’s pipeline encompasses diverse drug target classes, extending beyond the current landscape of immune checkpoints to include novel soluble and epigenetic checkpoints while continuing to innovate within the B7-family of receptors.

"Achieving selective therapeutic targeting of HHLA2 demonstrates our team’s profound understanding of its intricate structure-function relationship and the critical role that HHLA2 plays in tumor immune evasion. Our work highlights the strength of Conformation-X’s drug discovery platform," said Dr. Stephen Weeks, Sr. Director of Structural Biology and Biophysics.