On July 13, 2023 Calliditas Therapeutics AB (NASDAQ: CALT) (NASDAQ Stockholm: CALTX) ("Calliditas") reported interim data from the proof-of-concept Phase 2 trial in patients with squamous cell carcinoma of the head and neck (SCCHN) with its lead NOX 1 and 4 inhibitor product candidate, setanaxib (Press release, Calliditas Therapeutics, JUL 13, 2023, View Source [SID1234633233]). The analysis reflects encouraging early clinical progression-free survival (PFS) results and is supportive of the presumed anti fibrotic mode of action of setanaxib.

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The basis for the analysis consisted of a data set of 20 patients with recurrent or metastatic SCCHN, out of which 16 patients had evaluable tumor size and PFS related results. Twelve (12) patients had tumor biopsies before and after treatment that were evaluable for the biomarker analysis, which included transcriptomic analysis and also evaluated pathology markers such as SMA, Foxp3 regulatory T cells and PDL-1 CPS. Due to the small sample size and heterogeneity of the patient population, any inferences from the interim analysis should be treated with caution.

The transcriptomic analysis showed that the two top pathways impacted by the treatment were fibrosis-related signaling pathways (the Idiopathic Pulmonary Fibrosis Signaling Pathway and Hepatic Fibrosis/Hepatic Stellate Cell Activation Pathway), providing support for the presumed mode of action relating to modulation of activated (myofibroblastic) fibroblasts, as well as the ongoing clinical programs.

Pathology analysis showed preliminary evidence of an increase in immunological activity within tumors of patients treated with setanaxib, with favorable changes in Foxp3and PDL-1 CPS. As SMA levels at baseline were not balanced between the groups, and tumor biopsy samples were generally small, it was not possible to draw any conclusions regarding setanaxib’s impact on SMA reduction.

In terms of PFS, 7 out of the 16 evaluable patients were progression-free with either stable disease or partial response, out of which 6 were in the setanaxib arm and 1 was in the placebo arm. 6 of the 7 patients were still on the study drug at the time of the data read out with the longest period on drug being reported as 21 weeks, related to a patient in the setanaxib arm.

"Based on the encouraging clinical and transcriptomic results, data clearly support the continuation of the trial, which will read out on tumor size and progression free survival in the full trial population next year. Also, it is interesting that the transcriptomic results clearly pointed to beneficial impact on 2 fibrosis-related signaling pathways, supporting the presumed mode of action as well as our pipeline programs. We are excited about the potential of setanaxib in disease areas where today treatment options are limited" said CEO Renée Aguiar-Lucander.

"We are pleased with these encouraging interim data in a patient population where additional effective treatments are needed, and look forward to completing the study in collaboration with our excellent sites and investigators" said CMO Richard Philipson.

The trial is a randomized, placebo-controlled, double-blind, proof-of-concept Phase 2 study investigating the effect of setanaxib 800 mg twice daily in conjunction with pembrolizumab 200mg IV, administered every 3 weeks (an accepted standard treatment regimen for SCCHN), in at least 50 patients with moderate or high CAF-density tumors. A tumor biopsy is taken prior to randomization and then again after at least 9 weeks of treatment. Treatment will continue until unacceptable toxicity or tumor progression, as is typical for oncology trials. The study is expected to read out final data in 2024.

On July 13, 2023 Vigeo Therapeutics, a clinical-stage immuno-oncology company pioneering novel cancer therapies, reported that a complete response patient (CR) in Glioblastoma (GBM) cohort from first in human study VT1021-01 (NCT03364400) has now completed 3 full years of dosing with VT1021 (Press release, Vigeo Therapeutics, JUL 13, 2023, View Source [SID1234633232]). When joining the study in July of 2020 the patient had a recurrent case of GBM. After multiple cycles of dosing with VT1021, the tumor was no longer detectable. Now, after 3 years of dosing the tumor continues to be undetectable on regular MRI scans.

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"The Vigeo Team continues to be encouraged at how well this patient has responded to VT1021 therapy" said Jing Watnick, COO of Vigeo Therapeutics, "Vigeo is currently testing the potential of VT1021 therapy in both newly diagnosed and recurrent GBM patients as part of an ongoing phase II/III clinical study (NCT03970447)."

VT1021 is a first-in-class compound that, by binding to MDSCs, induces the expression of thrombospondin-1 (Tsp-1) in the tumor microenvironment (TME). Tsp-1 blocks the CD47 immune checkpoint and engages CD36 to induce tumor cell apoptosis, inhibit angiogenesis, activate cytotoxic T cells (CTL), and reprogram macrophages from the M2 to M1 phenotype. Vigeo recently reported the outcome of a GBM cohort of recurrent subjects treated with VT1021 as a single agent in which a group of 22 evaluable subjects with rGBM, 3 had a complete response (CR), 1 had a partial response (PR), and 6 had stable disease (SD) with an average study duration of over 120 days. Historically, rGBM patients have a response rate of less than 5% and a median progression free survival of 48 days.

About VT1021
Vigeo’s lead asset, VT1021, is a first-in-class dual-modulating compound that blocks the CD47 immune checkpoint and activates CD36, which induces apoptosis in tumors and endothelial cells, and increases the M1:M2 macrophage ratio. VT1021 achieves these biological effects via stimulation of thrombospondin-1 (Tsp-1). The goal of these dual-modulating effects is conversion of immuno-suppressive, or "cold," tumors that that are associated with poor response to immuno-oncology agents, to immuno-stimulated, or "hot," tumors that are more susceptible to attack from the body’s immune system. Vigeo is developing VT1021 as a therapeutic agent across a range of cancers, with a current focus on solid tumors.

On July 13, 2023 Menarini Silicon Biosystems (MSB), a pioneer in liquid biopsy and single cell technologies, reported the availability of its new CELLSEARCH CTC lab service to detect expression of the Delta-Like Ligand 3 (DLL3) protein in tumor cells circulating in the bloodstream (Press release, Menarini Silicon Biosystems, JUL 13, 2023, View Source [SID1234633231]). This biomarker is mainly expressed in difficult-to-treat cancers. The new MSB lab service opens the door to the development of further minimally invasive tests that leverage the prognostic and predictive value of biomarkers in medical settings with high unmet needs.

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According to Ralf Schoenbrunner, Chief Global R&D Officer of Menarini Silicon Biosystems, "We have the capability to develop such tests very quickly. This is important because new biomarkers are helping clinical researchers to determine treatment response in oncology trials, as well as guide physicians in their selection of therapies to improve outcomes in cancer patients. Making new biomarker assays quickly available is key to enable this progress."

Lung cancer is the second most common cancer worldwide with over 2.2 million cases in 2020. Small cell lung cancer (SCLC) represents about 15%[1] of these cancers and is more aggressive than the more prevalent Non-Small Cell Lung Cancer (NSCLC) and often diagnosed in the late stage of the disease. DLL3 is an inhibitory ligand of the Notch receptor whose overexpression on the surface of neuroendocrine neoplasms (NENs) is associated with the formation of high-grade neuroendocrine tumor types such as SCLC. The DLL3 biomarker is of great interest because it is highly expressed in the tumor tissue of patients with SCLC and other NENs but minimally in normal tissue. For this reason, scientists worldwide are increasingly investigating DLL3 proteins as they could represent clinically actionable targets.

CTCs in the bloodstream represent a premetastatic population involved in tumor dissemination. The fact that DLL3 positivity may be associated with more aggressive disease, strongly supports the clinical relevance of enumeration and characterization of CTCs that express this protein.

In addition, the new CELLSEARCH CTC test that detects this biomarker has the great advantage of being minimally invasive, standardized and allows for the dynamic real-time quantification of CTCs. It is based on the CELLSEARCH CTC platform, first and only clinically validated, FDA-cleared system for identification, isolation, and enumeration of CTCs in patients with metastatic breast, castration-resistant prostate or colorectal cancer. This is the first time that the CELLSEARCH platform is being made available for biopharma companies, who are focusing on developing treatments for lung cancer and other NENs.

According to Fabio Piazzalunga, President and CEO of Menarini Silicon Biosystems (MSB), "Our unique CELLSEARCH technology allows us to utilize any type of tumor protein marker to characterize CTCs. This broadens the portfolio of Menarini Silicon Biosystems’ commercially available assays and demonstrates this technology’s ability to accommodate other targets in which pharma companies may be interested."

CTC phenotypic characterization has the potential to not only support biopharma companies in their clinical development programs but in the future will also allow for decision making on personalized therapeutic strategies in an increasingly larger range of tumor types. This will help to avoid delays in needed therapies, minimize patient exposure to unnecessary medical strategies and reduce the high costs of inappropriate care.

On July 13, 2023 Plus Therapeutics, Inc. (Nasdaq: PSTV) (the "Company"), a clinical-stage pharmaceutical company developing targeted radiotherapeutics with advanced platform technologies for central nervous system cancers, reported that Marc Hedrick, M.D., President and Chief Executive Officer, will give two presentations at the Targeted Radiopharmaceuticals Summit taking place July 25-27, 2023 in Boston, Massachusetts (Press release, PLUS THERAPEUTICS, JUL 13, 2023, View Source [SID1234633230]).

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The presentations will describe data from the ReSPECT-GBM clinical study evaluating the Company’s lead radiotherapeutic, rhenium (186Re) obisbemeda, for the treatment of recurrent glioblastoma (rGBM), as well as provide an overview of the Company’s scientific approach, current pipeline and a snapshot of where it is headed.

Details of presentations:

Title Re-186 Radiolabelled NanoLiposomes for Rare Brain & Spinal Cord Tumors

Date July 26, 2023, 9:30 a.m. ET

Session Targeted Radiopharmaceuticals in the US: The Past, the Present & the Future



Title Novel Approaches to Central Nervous System Targeted Radiotherapeutics

Date July 26, 2023, 2:30 p.m. ET

Session Addressing TRP Toxicity: Chelators, Clearance & Drug Design

A copy of the presentations will be made available under the Presentations tab of the Investors section of the Company’s website following the meeting at View Source

On July 13, 2023 Theseus Pharmaceuticals, Inc. (NASDAQ: THRX) (Theseus or the Company), a clinical-stage biopharmaceutical company focused on improving the lives of cancer patients through the discovery, development, and commercialization of transformative targeted therapies, reported that it is discontinuing enrollment in the ongoing phase 1/2 study and terminating development of THE-630 in patients with gastrointestinal stromal tumors (GIST) (Press release, Theseus Pharmaceuticals, JUL 13, 2023, View Source [SID1234633228]).

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Theseus previously released initial dose escalation data from the ongoing phase 1/2 trial, which employs a standard 3 + 3 dose escalation design, on May 25, 2023. As of the April 21, 2023 data cutoff date, 23 patients had been dosed through Cohort 6 (18 mg) and 2 patients had been enrolled in Cohort 7 (27 mg). As of May 25, those 2 patients in Cohort 7 had cleared the dose-limiting toxicity (DLT) observation period without experiencing a DLT.

Following the data release on May 25, the third patient enrolled in Cohort 7 experienced grade 3 hand-foot skin reaction (HFSR), which required an expansion of the cohort to 6 patients. Subsequently, one of the patients enrolled in the Cohort 7 expansion group experienced grade 2 HFSR, which required a dose interruption of ≥7 days. Both the grade 3 HFSR and the grade 2 HFSR necessitating ≥7 days dose interruption were determined to be DLTs according to the study protocol. Therefore, with 2 out of 6 patients experiencing a DLT, the 27 mg dose exceeds the maximum tolerated dose (MTD). The Company does not believe that THE-630 has a differentiated profile at doses below 27 mg, which would provide exposure well below the target level of 100 nanomolar average concentration. As a result, the Company has made the decision to terminate the development of THE-630 in GIST. Patients currently enrolled in the trial will continue to receive THE-630 until a treatment discontinuation criterion is met.

As of July 10, 2023, 32 patients have been treated with THE-630 across 7 dose levels (3 mg to 27 mg). Six patients developed grade 1 to 3 HFSR (3 patients in the 27 mg cohort, 2 patients in the 18 mg cohort, and 1 patient originally in the 9 mg cohort after intra-patient dose escalation to 18 mg). Grade 3 HFSR was only observed in a patient who started treatment at 27 mg. HFSR was not observed at doses of 12 mg or lower. No significant skin toxicity was observed in preclinical toxicology studies. The Company is analyzing trial data to inform the feasibility of developing low dose THE-630 for KIT-associated mast cell-driven inflammatory indications, given its potent inhibition of wild-type KIT observed in preclinical assays.

Theseus has continued an extensive medicinal chemistry effort to target KIT, which has led to the discovery of a series of chemically distinct, highly selective, pan-variant KIT inhibitors for the treatment of early-line GIST. Theseus plans to nominate a development candidate from this series in the first half of 2024.

"We are disappointed that we will not be able to achieve the target exposure for pan-variant inhibition with THE-630, as we continue to believe a therapy with potent activity against all major classes of activating and resistance mutations in KIT has the potential to confer significant clinical benefit, given the unmet need in GIST," said Tim Clackson, Ph.D., President and Chief Executive Officer of Theseus. "On behalf of the entire Theseus team, I would like to thank the patients, their caregivers, and the investigators and site staff who participated in this study. We remain committed to helping GIST patients with plans to nominate a new, highly selective pan-variant KIT inhibitor candidate for GIST in the first half of 2024. Moving forward, we are excited to have THE-349 as our next near-term clinical program, with its potential best-in-class profile as a fourth generation EGFR inhibitor appropriate for both monotherapy and combination approaches."

Strategic Priorities:

· Advance THE-349 into clinical studies: THE-349 is a potentially best-in-class fourth-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) for the treatment of EGFR mutant non-small cell lung cancer.

o Preclinical data demonstrate THE-349 can potently inhibit all major classes of EGFR activating and resistance mutations observed in a post-first- or later-line osimertinib setting, possesses kinome and wild-type EGFR selectivity, and has central nervous system (CNS) activity.

o IND-enabling toxicology studies have been completed, and Theseus remains on track to submit an Investigational New Drug Application (IND) for THE-349 in the fourth quarter of 2023, and commence its clinical program as soon as possible thereafter, subject to clearance of the IND by the U.S. Food and Drug Administration.

· Advance BCR-ABL Program: Theseus aims to develop a potent and selective, next-generation, pan-variant BCR-ABL TKI candidate that optimizes the balance of safety and efficacy for patients with relapsed/refractory chronic myelogenous leukemia (CML) and patients with newly diagnosed Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL).

o Theseus plans to pursue clinical development in patients with CML who have been previously treated with a second-generation TKI or have the T315I mutation, and in newly diagnosed patients with Ph+ ALL.

o Theseus plans to nominate a development candidate for this program in the first half of 2024.

· Advance KIT program for GIST: KIT mutant GIST remains an area of major unmet medical need, requiring a pan-variant molecule to target all major activating and resistance mutations in KIT, with high selectivity, for use in early-line patients.

o Theseus has continued an extensive medicinal chemistry effort to target KIT which has led to the discovery of a series of chemically distinct, highly selective, pan-variant KIT inhibitors for the treatment of early-line GIST.

o Theseus plans to nominate a development candidate from this series in the first half of 2024.

· As of June 30, 2023, the Company had approximately $234 million in cash, cash equivalents, and marketable securities. Theseus expects its current cash, cash equivalents, and marketable securities to fund operations and capital expenditures into 2026 based on its current operating plan.