Mendus AB (publ) – ALISON trial data presented at ESMO Gynaecological Cancers demonstrate tumor-directed immune responses in the majority of patients treated with vididencel

On June 20, 2024 Mendus AB ("Mendus" publ; IMMU.ST), a biopharmaceutical company focused on immunotherapies targeting tumor recurrence, reported that updated clinical data from the ALISON clinical trial with its lead product vididencel in ovarian cancer will be presented at the ESMO (Free ESMO Whitepaper) Gynaecological Cancers Annual Congress, being held from June 20-22, 2024 in Florence, Italy (Press release, mendus, JUN 20, 2024, View Source [SID1234644451]). The trial reached its primary objective of inducing tumor-directed immune responses in at least 10 patients treated with vididencel.

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Ovarian cancer is the deadliest gynaecological cancer, mainly due to its high recurrence rate. Improving disease free and overall survival in advanced high grade serous ovarian carcinoma (HGSC) after primary treatment remains challenging. The Phase 1 ALISON trial explores the potential of vididencel to induce clinically relevant immune responses in ovarian cancer. The trial is fully enrolled (17 participants) and all participants have completed the vididencel treatment phase per April 2024. Vididencel-induced immune responses against tumor antigens that are regularly upregulated in HGSC were observed in 10 out of 15 patients evaluated so far, with 3 patients not reaching a vaccine induced response (VIR) due to high baseline responses. Vididencel treatment only gave mild adverse reactions, predominantly at the site of injection. The observed immune responses following vididencel treatment may provide the basis for an effective anti-tumor response. At week 22, 10 patients had stable disease and 7 patients had imaging-confirmed recurrence. To further evaluate clinical benefit, long-term follow-up of patients is ongoing.

Mendus anticipates to report the primary read-out of the ALISON trial based on immune response evaluation of all treated patients in 2024Q4.

Please see below for abstract details:

Abstract Number: 50P (poster presentation)

Abstract Title: Vididencel, a cell-based cancer vaccine, induces tumor-directed immune responses in high-grade serous ovarian carcinoma patients

Authors: A. Vledder, H. van Zeeburg, K. Brummel, A.L. Eerkens, N. van Rooij, A. Plat, J. Rovers, M. de Bruyn, H. Nijman

Session Date & Time: Thursday, 20 June 2024 between 12:30 – 13:30 CEST

After presentation, the poster will be made available on the Mendus website.

Tubulis Doses First Patient in Phase I/IIa Trial Investigating ADC Candidate TUB-040 in Ovarian Cancer and Lung Adenocarcinoma

On June 20, 2024 Tubulis reported that the first patient has been treated in its first Phase I/IIa trial (NAPISTAR 1-01, NCT06303505) (Press release, Tubulis, JUN 20, 2024, View Source [SID1234644467]). The study is evaluating Tubulis’ next-generation antibody-drug conjugate (ADC) TUB-040 in patients with platinum-resistant high-grade ovarian cancer (PROC) or relapsed/refractory adenocarcinoma non-small cell lung cancer (NSCLC), who have exhausted other available treatment options. TUB-040 targets NaPi2b, a highly overexpressed antigen in ovarian cancer and lung adenocarcinoma. The candidate is the first to enter the clinic from the company’s growing pipeline and represents one of Tubulis’ two lead candidates developed using its proprietary suite of platform technologies, which enable the creation of uniquely matched ADCs with superior biophysical properties.

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The multicenter, first-in-human, dose escalation and optimization Phase I/IIa study aims to investigate the safety, tolerability, pharmacokinetics, and efficacy of TUB-040 as a monotherapy. The trial will be conducted in the US as well as the UK, Spain, Belgium, and Germany. Phase Ia comprises the dose escalation and will determine safety and the maximum tolerated dose or the identified dose for optimization, whereas Phase IIa will focus on dose optimization, safety, and preliminary efficacy of TUB-040. The first patient has been dosed in the US following IND approval by the FDA.

"ADCs are beginning to show their potential as a core treatment modality replacing conventional chemotherapy for several solid tumor indications. Based on our preclinical data we are convinced that TUB-040 can represent a new option for the effective treatment of NSCLC and ovarian cancer patients," said Günter Fingerle-Rowson, MD, PhD, Chief Medical Officer at Tubulis. "The novel P5 technology we use in TUB-040 improves upon current limitations due to off-target toxicity and restricted durability, the main challenges of current ADC treatments. By achieving reduced non-target toxicity together with a more specific, more powerful, and continued on-tumor delivery of the payload, we aim to improve long-term anti-tumor responses and, ultimately, clinical outcomes for patients."

"Initiating our first clinical trial represents an important milestone for the entire Tubulis team and underscores our vision to innovate on all fronts of the ADC design for patient benefit," said Dominik Schumacher, PhD, Chief Executive Officer and Co-founder of Tubulis. "Our objective is to achieve clinical proof-of-concept for our lead candidate, TUB-040, and validate our differentiated platform approach to ADC development."

TUB-040 consists of a humanized, target-specific, Fc-silenced IgG1 antibody equipped with Tubulis’ proprietary Tubutecan linker-payload technology, which is based on P5 conjugation chemistry and the topoisomerase-1 inhibitor Exatecan. Tubulis recently presented a comprehensive preclinical data set at AACR (Free AACR Whitepaper), demonstrating the superior stability and minimal loss of linker-payload conjugation for their lead candidate. In a range of preclinical models, Tubulis was also able to show high and long-lasting anti-tumor responses, even at lower expression levels of NaPi2b, with an excellent safety and tolerability profile.

About TUB-040 and the P5 Technology

Tubulis’ lead antibody-drug conjugate (ADC) TUB-040 is directed against Napi2b, an antigen highly overexpressed in ovarian cancer and lung adenocarcinoma. It consists of an IgG1 antibody targeting Napi2b connected to the Topoisomerase I inhibitor Exatecan through a cleavable linker system based on the company’s proprietary P5 conjugation technology with a homogeneous DAR of 8. P5 conjugation is a novel chemistry for cysteine-selective conjugation that enables ADC generation with unprecedented linker stability and biophysical properties. It originated from the fundamental work of Prof. Christian Hackenberger at the Leibniz-Forschungsinstitut für Molekulare Pharmakologie im Forschungsverbund Berlin e.V. (FMP), which unlocked the use of phosphorus chemistry for superior bioconjugation. Preclinical pharmacokinetic analysis also demonstrated that TUB-040 efficiently delivers its payload to the tumor while reducing off-site toxicities. The candidate is currently being investigated in a multicenter Phase I/IIa study (NAPISTAR 1-01, NCT06303505) that aims to evaluate the safety, tolerability, pharmacokinetics, and efficacy of TUB-040 as a monotherapy.

TAE Life Sciences to Showcase Cutting-Edge Research at ICNCT 2024

On June 19, 2024 TAE Life Sciences reported a significant presence at the 20th International Congress on Neutron Capture Therapy (ICNCT), taking place in Krakow, Poland, from June 24 to 28, 2024 (Press release, TAE Life Sciences, JUN 19, 2024, View Source [SID1234644438]). This biennial event is the premier conference for advancements in the field of boron neutron capture therapy (NCT) and serves as a vital platform for researchers, clinicians, and industry professionals to share their latest findings and technological advancements in all aspects of BNCT.

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The 20th ICNCT conference will feature presentations, workshops, and discussions on various aspects of neutron capture therapy, including basic research, clinical applications, technological advances, materials and compounds, and case studies.

TAE Life Sciences’ Contributions at ICNCT 2024:

Plenary Presentation by CEO Rob Hill:
When: Wednesday, June 26 at 11:00 AM
Topic: State of TAE Life Sciences and BNCT Future Directions
Oral Presentations:
Tuesday, June 25 at 3:00 PM: Warren Kilby will present "Pharmacokinetic modeling to extrapolate from mouse to human biodistribution data for new tissues and compounds."
Wednesday, June 26 at 3:50 PM: Chad Lee will present "Neutron Beam System for Accelerator BNCT in China: Status and Performance."
Poster Presentations:
Tuesday, June 25 from 1:30 to 3:00 PM:
Michael Torgov will present in the Chemistry of NCT Carriers poster session about "Antibody boron conjugates with a payload comprised of carborane-modified poly-L-lysine is capable of delivering boron to EGFR-expressing tumor cells."
Karen Morrison will participate in the Biology poster session about "First reported immunohistochemical studies and q-PCR expression of LAT-1 transporter in the hamster cheek pouch oral cancer model."
Thursday, June 27 from 12:00 – 1:30 PM
Chad Lee will present in the Engineering and Physics poster session about "Optical monitoring of the position and size of direct current particle beams."
Warren Kilby will present in the Medical Physics poster session about "The expected dose of radiation therapists at a high-throughput BNCT Center."
TAE Life Sciences is proud to contribute to the advancement of neutron capture therapy and to be part of this esteemed conference. We look forward to engaging with other professionals in the field, sharing our research and innovations, and exploring collaborative opportunities to further enhance the
effectiveness and application of NCT in the field of oncology.

If you’re interested in learning more about our presence at ICNCT or are planning to attend and would like to meet with the team, please email Anna Theriault at [email protected].

Rutherrin® Demonstrates Complete Response in Lung Cancer Preclinically

On June 19, 2024 Theralase Technologies Inc. ("Theralase" or the "Company") (TSXV: TLT) (OTCQB: TLTFF), a clinical stage pharmaceutical company dedicated to the research and development of light and/or radiation activated small molecules and their formulations, intended for the safe and effective destruction of various cancers, bacteria and viruses, reported that it’s lead drug formulation, Rutherrin, has demonstrated an ability to provide a complete response in a Non-Small Cell Lung Cancer ("NSCLC") animal model (Press release, Theralase, JUN 19, 2024, View Source [SID1234644441]).

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Theralase recently press released its latest research, using a well-established Lewis Lung Cancer ("LLC1") orthotopic model, representing NSCLC. In this model, mouse lungs are implanted with lung cancer cells, inducing these mice to develop very aggressive, fast growing and metastatic lung tumors.

The mice were treated with x-ray radiation only as a control and x-ray activated Rutherrin as the active arm. The mice treated with x-ray activated Rutherrin demonstrated up to a 4-fold reduced tumor progression, based on Computerized Tomography ("CT") scan assessment of tumor volumes.

These results demonstrate that animals treated with a combination of Rutherrin and radiation therapy showed an increase in median survival from 26 to 35 days, versus radiation only. In scientific publications, mouse survival of 9 days has been equated to the equivalent of 1 year survival in humans, but more importantly, is that one animal treated with the x-ray activated Rutherrin (which had a positive lung tumor verified by CT scan) demonstrated a complete response and is now considered cancer free.

Dr. Arkady Mandel, M.D., Ph.D., D.Sc., Chief Scientific Officer of Theralase stated, "The latest preclinical research demonstrates the ability of x-ray activated Rutherrin to eradicate lung cancer in an animal model. This is initial research and through optimization, Theralase hopes to achieve a complete response in a much greater percentage of animals, but this initial data is extremely encouraging. As a result of this latest success, Theralase has committed to bringing this technology to market through the systematic research and development of this cutting-edge clinical therapy to safely and effectively destroy various cancers in patients. As a direct result, our list of cancer targets has increased from bladder cancer, which in the late stage of clinical development, to encompass brain cancer, lung cancer and various blood-based cancers, such as: leukemia, lymphoma and multiple myeloma."

Roger DuMoulin-White, B.E.Sc., P.Eng., Pro.Dir., President and Chief Executive Officer of Theralase stated, "This latest research symbolizes the significant progress Theralase has made over the last few years in the research and development of world-class systemic and targeted therapies for the treatment of various hard-to- treat cancers, such as: bladder cancer, brain and lung cancer. Pending sufficient capitalization and completion of a Good Laboratory Practice ("GLP") toxicology analysis for Rutherrin, Theralase plans to commence clinical studies for brain cancer, lung cancer and various blood-based cancers. If proven safe and effective in humans, Theralase hopes to change the paradigm of how patients diagnosed with cancer are treated in the future."

About Lung Cancer:

Lung cancer is the leading cause of cancer death worldwide. Most patients die of progressive metastatic disease despite aggressive local and systemic therapies. The survival rate for lung cancer depends on the type, stage and age of the patient, with the overall 5-year survival rate for all types of lung cancer about 26.6%. Lung cancer is histologically classified into two main types: Small Cell Lung Cancer ("SCLC"), which accounts for approximately 15% of the patients diagnosed with lung cancer and Non-Small Cell Lung Cancer ("NSCLC"), which accounts for approximately 85%.

Golidocitinib Approved in China as First-in-class JAK1 Only Inhibitor for the Treatment of Relapsed or Refractory Peripheral T-Cell Lymphoma

On June 19, 2024 Dizal (SSE:688192), a biopharmaceutical company committed to developing novel medicines for the treatment of cancer and immunological diseases, reported that the National Medical Products Administration of China has approved golidocitinib for the treatment of adult patients with relapsed or refractory (r/r) peripheral T-Cell lymphoma (PTCL) whose disease has progressed on or were refractory to at least 1 prior systemic therapy (Press release, Dizal Pharma, JUN 19, 2024, View Source [SID1234644442]). To date, golidocitinib is the first and only approved Janus kinase 1 (JAK1) selective inhibitor for r/r PTCL patients globally.

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PTCL is a heterogeneous group of aggressive T-cell/natural killer (NK) cell non-Hodgkin lymphomas (NHL). Patients with PTCL face an extremely high risk of disease relapse even if they achieved tumor remission following first-line conventional therapy. The outcome for relapsed or refractory patients is extremely poor, with a 3-year survival rate of 23% and a median overall survival (mos.) of 5.8 months. Although couple of drugs have been granted conditional approval by regulatory agencies in the relapsed or refractory setting, their single agent activities have been modest, with objective response rates (ORRs) lower than 30%.

Golidocitinib was approved based on findings from JACKPOT8 Part B (JACKPOT8B) study, the multinational pivotal study to evaluate the efficacy and safety of golidocitinib in r/r PTCL as a monotherapy. The primary endpoint was the objective response rate (ORR), assessed by an independent review committee (IRC). Full analysis of the study was simultaneously published in The Lancet Oncology and presented in oral session at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition.

In JACKPOT8B study, golidocitinib demonstrated superior and durable antitumor efficacy and a favorable safety profile in r/r PTCL patients, compared with existing treatment options. At the data cut-off date August 31, 2023, the ORR was 44.3% including a complete response (CR) rate of 23.9% per IRC. Tumor responses were observed across various PTCL subtypes. The median duration of response (mDoR) was 20.7 months and 53.8% of patients were still responding.

"Golidocitinib features novel mechanism and unique molecular design, positioning it as the first oral JAK1 only inhibitor for the treatment of r/r PTCL. Multiple studies have clearly demonstrated its favorable pharmacokinetic properties and significant clinical benefit," said Jun Zhu, MD, PhD at the Department of Lymphoma, Peking University Cancer Hospital and Institute, the leading principal investigator of the JACKPOT8B study, "Golidocitinib achieved an ORR of 44.3% and a DoR of 20.7 months in r/r PTCL. It’s approval and market launch provide a much needed option for doctors to treat PTCL patients."

Dizal was the first to identify and validate targeting the JAK/STAT pathway as a promising therapeutic approach for PTCL, leading to the development of golidocitinib as the world’s first JAK1 only inhibitor. With > 200 to 400-fold selectivity over other JAK family members and ideal pharmacokinetic properties, golidocitinib exerts potent antitumor efficacy with a favorable safety profile.

"We are thrilled to bring golidocitinib, the world’s first JAK1 only inhibitor, to patients in China, marking the second approved innovative drug from Dizal," said Xiaolin Zhang, PhD, CEO of Dizal. "Golidocitinib yields good antitumor efficacy across different subtypes of PTCL, which differentiate golidocitinib from other targeted therapies. At Dizal, we aspire to discover and develop first-in-class and groundbreaking new medicines to address unmet medical needs around the world. With the US FDA Fast Track designation, we are expediting global development of golidocitinib to bring this exciting drug to patients worldwide."

With superior efficacy and safety profile, golidocitinib has been widely acknowledged at prestigious international congresses including ASCO (Free ASCO Whitepaper), EHA (Free EHA Whitepaper), ICML, and ASH (Free ASH Whitepaper), with six oral presentations over four consecutive years. The results of the multinational study JACKPOT8 were published in Annals of Oncology and The Lancet Oncology.

About golidocitinib (DZD4205)

Golidocitinib is currently the first and only Janus kinase 1 (JAK1) selective inhibitor being evaluated for the treatment of r/r PTCL. In June 2024, golidocitinib was approved by the National Medical Products Administration (NMPA) of China for the treatment of adult patients with relapsed or refractory peripheral T-cell lymphoma (r/r PTCL).

At the data cut-off date of August 31, 2023, golidocitinib has demonstrated robust and durable anti-tumor efficacy, with an ORR of 44.3%. More than 50% of the patients with tumor remission achieved a complete response with a CRR of 23.9%. Per IRC assessment, mDoR reached 20.7 months. Golidocitinib was granted Fast Track Designation by the U.S. FDA for the treatment of r/r PTCL in February 2022. In September 2023, the CDE accepted its NDA and granted Priority Review for the treatment of r/r PTCL. The Phase I clinical data of golidocitinib (JACKPOT8 PART A) was published in Annals of Oncology (Impact Factor: 51.8), and global pivotal trial data of golidocitinib for the treatment of r/r PTCL (JACKPOT PART B) was published in The Lancet Oncology (Impact Factor: 54.4).