On July 13, 2023 TME Pharma N.V. (Euronext Growth Paris: ALTME), a biotechnology company focused on developing novel therapies for treatment of cancer by targeting the tumor microenvironment (TME), reported a positive clinical update on the best response to therapy, reporting one patient achieving complete response in the GLORIA expansion arm evaluating NOX-A12, TME Pharma’s CXCL12 inhibitor, in combination with standard of care radiotherapy and anti-VEGF, bevacizumab, in first-line glioblastoma (Press release, TME Pharma, JUL 13, 2023, View Source [SID1234633236]).

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One patient (out of 6) in the expansion arm with a previous best response of 89.9% tumor shrinkage has achieved complete response, meaning the tumor disappeared completely and was no longer detectable by MRI. The complete response comes in addition to 2 patients with reported near-complete reductions (>99%) in tumor size, leading to 50% of patients in the GLORIA trial expansion arm achieving a complete or near-complete response.

"We are very pleased to report this highly positive update from the expansion arm of our GLORIA clinical trial evaluating our lead asset NOX-A12 in combination with radiotherapy and bevacizumab in glioblastoma," said Aram Mangasarian, CEO of TME Pharma. "It is very encouraging to see one patient achieve no detectable tumor and two patients coming extremely close to complete response, achieving a reduction in tumor size of more than 99 percent. This complete response took about 12 months of therapy to achieve, underlining the importance of mature data to fully evaluate the power of NOX-A12-based therapy. Taken together with the promising picture emerging from our survival data, it is becoming clearer that NOX-A12 used in this treatment combination can provide clinically meaningful benefit over standard of care for brain cancer patients, who currently have such limited therapeutic options."

The latest survival data reported from the GLORIA expansion arm demonstrated that after 15 months on study (median), 83% of patients (5 of 6) are still alive. As long as treatment or follow-up for these patients is ongoing, median overall survival (mOS) will continue to improve1. As a reference, the expected median overall survival for patients under current standard of care with chemotherapy refractory tumors (MGMT unmethylated) and whose tumor remains detectable after surgical intervention is approximately 10 months2.

In November 2022, TME Pharma announced interim results from the GLORIA expansion arm that demonstrated:

100% of target lesions treated with the triple combination of NOX-A12, radiotherapy and bevacizumab were reduced by more than 50% as measured by MRI.
5 of 6 patients (83%) achieved durable partial responses (PR) by mRANO criteria3, which take into account radiographic response as well as other factors such as the clinical condition of the patient. One patient experienced progressive disease (PD) due to distant failure while target lesion control was maintained.
The triple combination was well tolerated and safe. No dose-limiting toxicities were observed.

On July 13, 2023 KSQ Therapeutics, Inc. ("KSQ"), a clinical-stage biotechnology company developing cancer therapies using its proprietary CRISPRomics discovery platform, reported that it has entered into a worldwide license and collaboration agreement with Roche for the development and commercialization of KSQ-4279 (Press release, KSQ Therapeutics, JUL 13, 2023, View Source [SID1234633235]). KSQ-4279 is a first-in-class, potent, and selective small molecule inhibitor of USP1, a protein that regulates DNA damage response (DDR) in a manner distinct from other approaches, including PARP inhibitors. The molecule is currently in a Phase 1 clinical trial for the treatment of solid tumors. Under the collaboration, Roche will assume development responsibilities for KSQ-4279, which has the potential to treat a variety of cancers.

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"We believe KSQ-4279, which was discovered through our proprietary CRISPRomics platform, has incredible potential to help patients with a variety of solid tumors based on the strong preclinical data we have seen to date. We are confident Roche is the right partner to further the development of KSQ-4279 and maximize its benefits for patients," said Qasim Rizvi, Chief Executive Officer of KSQ. "For KSQ, this agreement enables us to fully focus our attention on advancing our own immunotherapy programs and to continue leveraging our successful platform to discover novel targets."

"DDR is a promising and emerging area of research in oncology," said James Sabry, M.D., Ph.D., Global Head of Pharma Partnering, Roche. "We are excited to collaborate with KSQ on their novel inhibitor of USP1 as a potential new treatment option for patients with significant unmet medical needs across a range of cancers. This partnership reflects our strategic focus of fitting treatments to patients and delivering personalized healthcare."

Under the terms of the agreement, KSQ will receive an upfront payment and will be eligible to receive additional milestone and royalty payments. KSQ grants Roche a global license wherein Roche will be fully responsible for the further development of KSQ-4279 in 2024.

KSQ-4279

KSQ-4279 is a first-in-class small molecule inhibitor of USP1, a protein regulating DNA damage response (DDR). USP1 was identified by KSQ’s CRISPRomics platform as an attractive cancer target with established roles in DNA damage repair processes that are distinct from PARP inhibitors and other approaches currently being tested in the clinic. KSQ-4279 is currently in a Phase 1 clinical trial (KSQ-4279-1101) in patients with advanced solid tumors. It is a dose-escalation and expansion trial of KSQ-4279 as a monotherapy and in combination.

On July 13, 2023 Nona Biosciences, a wholly-owned subsidiary of HBM Holdings Limited, committed to cutting-edge antibody technology innovation and provider of integrated solutions from "Idea to IND" (I to ITM) announced that, DualityBio, a collaborator of Nona Biosciences, and BeiGene entered into an agreement for BeiGene to acquire an exclusive option for a global clinical and commercial license to an investigational, preclinical ADC program for patients with select solid tumors. This program was developed under the collaboration agreement commenced between Nona Biosciences and DualityBio.

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Nona Biosciences entered into a collaboration agreement with DualityBio in 2022, pursuant to which Nona Biosciences granted the exclusive rights of its monoclonal antibodies for specific tumors to DualityBio to develop the world’s first-in-class ADC. The collaboration between Nona Biosciences and DualityBio will continue in accordance with the terms of the collaboration agreement.

Nona Biosciences has established considerable experience and expertise in ADC field. While continuously optimizing its advanced platform technology, Nona Biosciences has actively established an ADC cooperation ecosystem and closely cooperated with multiple innovation pioneers, to fully unleash its innovation capability and accelerate the innovations of novel ADC therapeutics globally. Nona Biosciences will further expand its networks in ADC innovation as one of its core strategies, continue to enhance the value of innovation, and fulfill global medical needs.

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.