On April 9, 2024 Syntara Limited (ASX: SNT) reported that it has reached the 50% recruitment milestone in its Phase 2 trial evaluating SNT-5505, in combination with ruxolitinib, treating the bone marrow cancer myelofibrosis (Press release, Syntara, APR 9, 2024, View Source [SID1234641950]).

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Recruitment for the open-label study commenced in December 2023 with the 8th patient in the 15-patient trial dosed earlier this week, keeping Syntara on track for completion of recruitment by the end of H1 2024.

The trial is being conducted across 19 clinical trial sites in the USA, Australia, South Korea and Taiwan. SNT-5505 is a pan-LOX inhibitor and the lead asset in Syntara’s drug discovery pipeline.

Syntara anticipates reporting on 6-month results of the trial in an interim data update at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in December 2024. The interim data is expected to allow Syntara to engage with and discuss pivotal study design with the FDA in Q1 2025, with the full 12-month data set to be available by mid-2025.

Syntara commenced the combination trial after it found encouraging efficacy and an excellent safety profile in a Phase 2 monotherapy trial of the drug, as presented at ASH (Free ASH Whitepaper) in December 2023. An effective pan-LOX inhibitor, such as SNT-5505, for myelofibrosis has Syntara’s lead asset SNT-5505 reaches 50% recruitment in Phase 2 trial; interim results expected December 2024 2 disease modifying potential for patients and would unlock a market conservatively estimated to be more than $1 billion per annum.

Syntara CEO Gary Phillips said: "We’re very pleased with the progression of recruitment in this trial as we observe the impact SNT-5505 can have in combination with the approved standard of care ruxolitinib. In addition to providing us with an opportunity to discuss a pivotal registration study with the FDA, positive developments in the trial will provide Syntara with a platform to engage with potential partners that would be complementary to our efforts to commercialise the drug."

This combination cohort of the Phase 2 MF-101 trial aims to demonstrate that SNT-5505 is safe and effective in myelofibrosis patients who are sub optimally controlled on the market leading JAK inhibitor, ruxolitinib.

SNT-5505 has previously demonstrated compelling pre-clinical data when used in combination with standard of care in other haematological malignancies such as myelodysplastic syndrome and solid tumours like those found in hepatocellular carcinoma and pancreatic cancer.

On April 9, 2024 Transgene (Euronext Paris: TNG), a biotech company that designs and develops virus-based immunotherapies for the treatment of cancer, and NEC Corporation (NEC; TSE: 6701), a leader in IT, network and AI technologies, reported that new data will be presented on TG4050, an individualized neoantigen cancer vaccine, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in San Diego, CA (Press release, Transgene, APR 9, 2024, View Source [SID1234641949]). These data are highlighted in the AACR (Free AACR Whitepaper) press conference being held today and in a poster presentation which will take place tomorrow, April 10, at 9:00 a.m. PDT.

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TG4050 is based on Transgene’s myvac platform and powered by NEC’s cutting-edge AI capabilities designed to optimize antigen selection.

Key findings of the poster include:

-All 16 patients who received TG4050 are disease free after a median 18.6-month follow-up. Out of the 16 patients in the control observation arm, 3 patients have relapsed. For this head and neck cancer patient population and with current standard of care, approximately 40% of patients are expected to relapse within 24 months following surgery and adjuvant therapy (chemoradiotherapy). Also, the tumor immune contexture, expression of immune factors, mutational burden, and tumor infiltrates are associated with challenging prognoses.

-Specific cellular immune responses (CD8+ and CD4+) were detected in the 16/17 patients who received TG4050 (16 patients in the treatment arm and one patient from the observation arm treated after relapse) using stringent testing criteria. Immunogenicity or the capacity of treatment to induce immune responses are key to prevent relapses.

-TG4050 induced persistent immune responses against multiple targets in several patients. T cell responses were maintained beyond 211 days (7 months) after the initiation of the treatment. The duration of the immune response is also a key factor to fight disease over time.

Alessandro Riva, Chairman and CEO of Transgene, commented:

"We are honored by AACR (Free AACR Whitepaper)’s interest in the Phase I data generated from our individualized cancer vaccine TG4050. It is exciting to note that all patients who received TG4050 remain disease-free after a median follow-up of 18.6 months, which compares favorably to the observational arm which saw 3 out of 16 patients relapse during the same period."

"More importantly, almost all treated patients developed a specific immune response against the antigen targets we selected, providing robust proof of principle for our lead candidate. TG4050 is now starting to show a potential benefit for head and neck cancer patients at high risk of relapse. We look forward to starting the Phase II part of the trial in the adjuvant setting for head and neck cancer."

Dr. Oliver Lantz, Head of the clinical immunology laboratory at Institut Curie, added:

"The immunological data generated by TG4050 demonstrate a robust and specific cellular immune response, even under stringent measurement criteria. The diversity, depth and duration of these responses were most certainly a key factor in preventing relapse in the patients treated with TG4050."

Masamitsu Kitase, Corporate SVP and Head of the Healthcare and Life Sciences Division at NEC, concluded:

"Our state-of-the-art proprietary artificial intelligence and machine learning models have allowed us to identify immunogenic and clinically relevant mutations in all head and neck cancer patients for this TG4050 randomized Phase I trial. These tumors were characterized by a low tumor mutation burden, which presents an obstacle to designing a relevant vaccine. Our powerful platform enables us to identify mutations for individualized treatments which have now shown the first signs of clinical benefit for patients. Together with Transgene, we look forward to continuing to build on these promising data through our planned Phase II trial in the adjuvant treatment of head and neck cancer."

TG4050 is being evaluated in a randomized multicenter Phase I/II trial as a single agent in the adjuvant treatment of HPV-negative head and neck cancers (NCT04183166). Based on promising data obtained in the Phase I part of the trial, Transgene and NEC are preparing a randomized Phase II extension of this trial slated to start in the second quarter of 2024.

The poster can be viewed in-person during the poster presentation at the AACR (Free AACR Whitepaper) 2024 meeting and accessed on Transgene’s website.

On April 9, 2024 Molecular Templates, Inc. (Nasdaq: MTEM, "Molecular Templates," or "MTEM"), a clinical-stage biopharmaceutical company focused on the discovery and development of proprietary targeted biologic therapeutics, engineered toxin bodies ("ETBs"), to create novel therapies with potent differentiated mechanisms of action for cancer, reported that MTEM will present a poster, "First-in-human, dose escalation and expansion study of MT-6402, a novel engineered toxin body (ETB) targeting PD-L1, in patients with PD-L1 expressing relapsed/refractory advanced solid tumors: Interim Data," at the 2024 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting taking place in San Diego, CA, and also announced monotherapy response activity in Head and Neck Cancer (Press release, Molecular Templates, APR 9, 2024, View Source [SID1234641948]).

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The poster highlighted the following findings from the phase I dose-escalation study of MT-6402:

MT-6402 has been well tolerated with no drug-related Grade 4 or Grade 5 adverse events observed
MT-6402 acts uniquely from other approved checkpoint agents. MT-6402 depletes immunosuppressive PD-L1+ immune cells and tumor cells, activates a T-effector phenotype, and remodels the tumor microenvironment to restore T-cell surveillance of the tumor.
An early monotherapy efficacy signal in head and neck squamous cell carcinoma (HNSCC) was identified. Nine patients with recurrent and metastatic heavily pre-treated and checkpoint-experienced HNSCC were treated in the phase I dose escalation of which two patients have confirmed durable PRs.

2 of the 9 patients with HNSCC treated with MT-6402 showed confirmed partial responses (one response was unconfirmed at the time of the poster’s submission but has subsequently been confirmed). The patients remain on study at cycles 19 and 10, respectively (one cycle = 4 weeks), demonstrating the potential for durable monotherapy activity with MT-6402.
Both patients had low PD-L1 tumor expression and had progressed after multiple lines of therapy including checkpoint. Additionally, both patients showed unique pharmacodynamic effects consistent with tumor microenvironment remodeling including reduction in myeloid derived suppressor cells (MDSCs) and modulation of VEGF.
Tumor reductions were observed in other patients including an unconfirmed PR.
"We are excited to see objective responses in heavily pre-treated, checkpoint-experienced, head and neck cancer patients, a setting with high unmet medical need," said CEO Eric Poma. "The long-lasting partial responses were in patients with low PD-L1 expression and showed concomitant increases in cytokines associated with T-cell activation and tumor microenvironment remodeling not seen with other checkpoint therapies. We believe the novel mechanism of action of MT-6402 may allow for durable, T-cell-mediated, monotherapy activity in patients who have progressed on checkpoint therapy. Based on the preliminary signals of single agent activity with MT-6402, an expansion study in low PD-L1 head and neck cancer patients to further evaluate MT-6402 has been initiated."

AACR Presentation
Title: First-in-human, dose escalation and expansion study of MT-6402, a novel engineered toxin body (ETB) targeting PD-L1, in patients with PD-L1 expressing relapsed/refractory advanced solid tumors: Interim Data
Location: Section 48, Poster #19, Abstract #CT191
Date/Time: 9am – 12:30pm PT Tuesday, April 9, 2024
The abstract will be available in the Presentations section of MTEM’s website.

On April 9, 2024 Molecular Templates, Inc. (Nasdaq: MTEM, "Molecular Templates," or "MTEM"), a clinical-stage biopharmaceutical company focused on the discovery and development of proprietary targeted biologic therapeutics, engineered toxin bodies ("ETBs"), to create novel therapies with potent differentiated mechanisms of action for cancer, reported that MTEM will present a poster, "First-in-human, dose escalation and expansion study of MT-6402, a novel engineered toxin body (ETB) targeting PD-L1, in patients with PD-L1 expressing relapsed/refractory advanced solid tumors: Interim Data," at the 2024 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting taking place in San Diego, CA, and also announced monotherapy response activity in Head and Neck Cancer (Press release, Molecular Templates, APR 9, 2024, View Source [SID1234641948]).

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The poster highlighted the following findings from the phase I dose-escalation study of MT-6402:

MT-6402 has been well tolerated with no drug-related Grade 4 or Grade 5 adverse events observed
MT-6402 acts uniquely from other approved checkpoint agents. MT-6402 depletes immunosuppressive PD-L1+ immune cells and tumor cells, activates a T-effector phenotype, and remodels the tumor microenvironment to restore T-cell surveillance of the tumor.
An early monotherapy efficacy signal in head and neck squamous cell carcinoma (HNSCC) was identified. Nine patients with recurrent and metastatic heavily pre-treated and checkpoint-experienced HNSCC were treated in the phase I dose escalation of which two patients have confirmed durable PRs.

2 of the 9 patients with HNSCC treated with MT-6402 showed confirmed partial responses (one response was unconfirmed at the time of the poster’s submission but has subsequently been confirmed). The patients remain on study at cycles 19 and 10, respectively (one cycle = 4 weeks), demonstrating the potential for durable monotherapy activity with MT-6402.
Both patients had low PD-L1 tumor expression and had progressed after multiple lines of therapy including checkpoint. Additionally, both patients showed unique pharmacodynamic effects consistent with tumor microenvironment remodeling including reduction in myeloid derived suppressor cells (MDSCs) and modulation of VEGF.
Tumor reductions were observed in other patients including an unconfirmed PR.
"We are excited to see objective responses in heavily pre-treated, checkpoint-experienced, head and neck cancer patients, a setting with high unmet medical need," said CEO Eric Poma. "The long-lasting partial responses were in patients with low PD-L1 expression and showed concomitant increases in cytokines associated with T-cell activation and tumor microenvironment remodeling not seen with other checkpoint therapies. We believe the novel mechanism of action of MT-6402 may allow for durable, T-cell-mediated, monotherapy activity in patients who have progressed on checkpoint therapy. Based on the preliminary signals of single agent activity with MT-6402, an expansion study in low PD-L1 head and neck cancer patients to further evaluate MT-6402 has been initiated."

AACR Presentation
Title: First-in-human, dose escalation and expansion study of MT-6402, a novel engineered toxin body (ETB) targeting PD-L1, in patients with PD-L1 expressing relapsed/refractory advanced solid tumors: Interim Data
Location: Section 48, Poster #19, Abstract #CT191
Date/Time: 9am – 12:30pm PT Tuesday, April 9, 2024
The abstract will be available in the Presentations section of MTEM’s website.

On April 9, 2024 Zentalis pharmaceuticals presented its corporate presentation (Presentation, Zentalis Pharmaceuticals, APR 9, 2024, View Source [SID1234641946]).

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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