On August 27, 2024 Transgene (Euronext Paris: TNG), a biotech company that designs and develops virus-based immunotherapies for the treatment of cancer, reported the publication in the Journal for ImmunoTherapy of Cancer (JITC) of a peer-reviewed article which illustrates that TG6050 induces profound immune remodeling of the tumor microenvironment in animal models (Press release, Transgene, AUG 27, 2024, View Source [SID1234646104]). The paper highlights TG6050’s potential to induce sustained intratumoral expression of interleukin-12 (IL-12) and anti-cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) antibody at active concentrations without the toxicity observed with systemic administration.

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TG6050 is an oncolytic virus derived from Transgene’s invir.IO platform encoding interleukin-12 (IL-12) and an anti-CTLA4 antibody, with the potential to trigger a powerful localized antitumor immune response.

The JITC paper reports that in addition to consistent multiplication and propagation of TG6050 in tumor cells, functional transgenes are expressed in the tumor with a sustained intratumoral accumulation of IL-12 and anti-CTLA-4 antibody. The three components of TG6050 (oncolytic viral backbone, IL-12 and anti-CTLA-4 antibody transgenes) act together to induce tumor regression in numerous "hot" and "cold" murine tumor models investigated in these studies. This antitumoral activity was further amplified when TG6050 was combined with an anti-PD1.

Moreover, these studies show that TG6050 triggers a strong adaptive antitumoral immune response, accompanied by a profound modification of the tumor microenvironment based on infiltration of both innate and adaptive immune cells, altering it to a more inflamed state (from "cold" to "hot").

TG6050 was also shown to be safe. Upon intravenous administration in non-human primates for toxicology evaluation, it did not induce any of the IL-12 related adverse effects that are associated with systemic administration. TG6050 has now progressed into Phase 1 clinical development (the Delivir trial) in metastatic non-small cell lung cancer (NCT05788926).

"These strong preclinical data demonstrate the ability of our invir.IO oncolytic virus platform to generate promising candidates for further development and support our decision to advance TG6050 into the clinic in metastatic non-small cell lung cancer. We have thoroughly explored the mechanism of action of TG6050, with local delivery of functional IL-12 and anti-CTLA-4 resulting in strong antitumor activity. Moreover, in toxicology studies after repeated intravenous administrations in non-human primates, TG6050 did not display any observable adverse effects," commented Dr. Maud Brandely, MD, PhD, Chief Medical Officer of Transgene.

The JITC paper is titled "TG6050, an oncolytic vaccinia virus encoding interleukin-12 and anti-CTLA-4 antibody, favors tumor regression via profound immune remodeling of the tumor microenvironment" and can be accessed here.

About TG6050

TG6050 is an oncolytic virus developed with Transgene’s invir.IO platform for intravenous administration. invir.IO viruses are based on the patented large capacity Vaccinia virus Copenhagen strain genetically modified with the double deletion TK-RR- (VVCOPTK-RR-). TG6050 has been engineered to encode human IL-12, a cytokine that triggers a powerful antitumor immune response and a full length anti-CTLA4 antibody. It has also been optimized with the deletion of the gene encoding for the M2L viral protein that targets CD80 and CD86, two ligands of CD28 [source: Kleinpeter et al., J Virol. 2019 Jun 1 ; 93(11) : e00207-19]. The use of an oncolytic virus to deliver these immunotherapies locally and selectively in the tumor microenvironment allows high intratumoral concentrations of both therapeutic proteins eliciting a stronger and more effective antitumor response. By reducing systemic exposure to a very low level, this local therapeutic activity furthermore allows an increase in the safety and tolerability profile of IL-12 and the anti-CTLA4 antibody.

TG6050 is being evaluated in the Deliver trial, a Phase I trial conducted in advanced non-small cell lung cancer (NSCLC) patients.

About the Delivir trial (NCT: 05788926)

The Delivir trial is a multicenter, open label, dose-escalation Phase I trial evaluating TG6050 as a single agent. The trial will enroll up to 36 patients with metastatic/advanced NSCLC, who have failed standard therapeutic options including immunotherapies such as immune checkpoint inhibitors. Patients will receive single and repeated escalating doses of TG6050 administered intravenously, to determine the recommended dose and best schedule of administration for subsequent clinical development.

On August 27, 2024 Astellas Pharma Inc. (TSE: 4503, President and CEO: Naoki Okamura, "Astellas") reported dosing of the first patient in the HIGHLIGHT 1 Phase 3 pivotal study for fezolinetant, an investigational oral, nonhormonal compound being studied for the treatment of moderate to severe vasomotor symptoms (VMS) in women with breast cancer receiving adjuvant endocrine therapy (Press release, Astellas, AUG 27, 2024, View Source [SID1234646103]).

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Breast cancer is the most common cancer in women globally, with approximately 2.3 million new cases in 2022.1 Hot flashes and night sweats, also known as VMS, are recognized as the most prominent side effect of adjuvant endocrine therapies used in the treatment of breast cancer. Approximately 77% of breast cancers can be treated with adjuvant endocrine therapies,2 most commonly tamoxifen and aromatase inhibitors, and up to 97% of breast cancer patients experience hot flashes or night sweats.3

Marci English, Vice President, Head of BioPharma Development, Astellas
"VMS can adversely affect quality of life, as well as compliance with treatment, for patients with breast cancer taking adjuvant endocrine therapy. We are excited to get the HIGHLIGHT 1 study underway, as currently there are no approved treatments for moderate to severe VMS that can be used by these patients."

About HIGHLIGHT 1
HIGHLIGHT 1 (NCT06440967) is a randomized, placebo-controlled, double-blind, Phase 3 clinical study to assess the efficacy and safety of fezolinetant for the treatment of moderate to severe VMS in women with stage 0 to 3 hormone receptor-positive breast cancer who are receiving adjuvant endocrine therapy. Approximately 540 participants are planned to be randomized 1:1 to fezolinetant or placebo at up to 100 sites globally. The four coprimary endpoints are change in the frequency and severity of moderate to severe VMS from baseline to weeks 4 and 12. Patients will be treated for 52 weeks with a final evaluation at 55 weeks.

About Fezolinetant
Fezolinetant is an investigational oral, nonhormonal medicine in clinical development for the treatment of moderate to severe vasomotor symptoms (VMS) in women with breast cancer receiving adjuvant endocrine therapy. The safety and efficacy of fezolinetant have not been established in this patient population. VMS are also known as hot flashes or night sweats. Fezolinetant works by blocking neurokinin B (NKB) binding on the kisspeptin/neurokinin/dynorphin (KNDy) neuron, helping restore the balance in the brain’s temperature control center (the hypothalamus) to reduce the number and intensity of hot flashes and night sweats.4,5,6 There is no guarantee the agent will receive regulatory approval or become commercially available for the uses being investigated.

On August 26, 2024 The South Korean biotech company GI Innovation reported that it has signed a clinical trial collaboration and supply agreement with MSD (a tradename of Merck& Co., Inc., Rahway, NJ, USA) to evaluate the combination of GI-102 and MSD’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab) in patients with immunotherapy-resistant liver cancer, melanoma, and renal cell carcinoma (Press release, GI Innovation, AUG 26, 2024, View Source [SID1234646110]).

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This agreement marks GI Innovation’s second clinical trial collaboration with MSD, following a previous collaboration for GI-101A.

The Phase 2 clinical trial including GI-102 in combination with KEYTRUDA will enroll patients with resistance or non-response to immuno-oncology treatments, leaving them with no further treatment options. GI Innovation is focused on three indications with significant market potential and potential likelihood of success: metastatic liver cancer, melanoma, and renal cell carcinoma. The company has already demonstrated strong anti-cancer efficacy with a 42.9% overall response rate (ORR) in a monotherapy trial of GI-102 in melanoma patients who failed to respond to standard-of-care treatment (3 partial responses out of 7 patients). Complete tumor regression was previously observed in 60% of mice treated with GI-102 monotherapy in a preclinical liver cancer model.

Fourteen hospitals in South Korea and world-renowned sites in the U.S. have agreed to join the trial, including the Mayo Clinic (campuses in Rochester, Florida, and Arizona), Cleveland Clinic and Memorial Sloan Kettering Cancer Center. In South Korea, the trial will take place at leading hospitals including Samsung Medical Center, Asan Medical Center, Seoul National University Hospital, Severance Hospital of Yonsei University, and St. Vincent’s Hospital.

"We are pleased to enter into another clinical trial collaboration and supply agreement with MSD, a world leader in immuno-oncology. We aim to maximize the therapeutic value of GI-102 by combining it with KEYTRUDA, MSD’s anti-PD-1 therapy", said Dr Myung-Ho Jang, GI Innovation’s Chief Scientific Officer.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway NJ, USA.

On August 26, 2024 Diakonos Oncology Corp., a clinical-stage immuno-oncology company, reported the final closing of an oversubscribed seed financing of $11.4 million (Press release, Diakonos Oncology, AUG 26, 2024, View Source [SID1234646109]). The round was led by biotechnology investment firm Restem Group Inc., with participation from existing investors.

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To date, funds have enabled the company to establish manufacturing operations, add key leadership positions, and complete enrollment for the Phase 1 study of lead asset DOC1021 in the treatment of glioblastoma (GBM). The additional capital will fund operations into late 2025 and allow Diakonos to initiate the Phase 2 trial in GBM prior to closing a Series A round.

"We greatly appreciate the support of these investors in sharing our passion for improving the lives of patients suffering from deadly cancers such as glioblastoma," said Mike Wicks, Diakonos CEO. "The fact that this financing is nearly triple our initial target also shows they share our confidence in the effectiveness of our unique cancer therapy. This investment will fund operations through the final readout of key safety and efficacy data from our Phase 1 trial and will allow the company to ramp up preparations for pipeline expansion and the initiation of our Phase 2 GBM trial which is expected to begin in the fourth quarter of this year."

"We are thrilled to invest in this groundbreaking company that is at the forefront of cancer treatment innovation. As a firm deeply involved in the cell therapeutic field, we recognize the immense potential of their pioneering work with dendritic cell therapies and we are confident that this can become a new standard of care for cancer in the future," said Andres Isaias, Executive Chairman of Restem Group Inc.

About DOC1021

DOC1021 is a first-of-its-kind dendritic cell vaccine (DCV) that initiates a complete cytotoxic TH1 immune response against a patient’s cancer through our proprietary double loading technology. Enrollment in the two-year Phase 1 trial was completed in December 2023.

In addition to the lead GBM study, two other clinical trials of Diakonos’ DCV are ongoing for the treatment of pancreatic cancer and angiosarcoma. Diakonos has received Fast Track designations from the FDA for both the GBM and pancreatic cancer programs. The company has also received Orphan Drug Designation for the GBM program.

Diakonos’ DCVs activate robust cytotoxic TH1 cell signaling pathways that better harness a patient’s immune system to target and eliminate cancer cells. This is achieved without any genetic modification of the patient’s immune cells and without the need for toxic preconditioning.

On August 26, 2024 Opna Bio reported that it has dosed the first patient with OPN-6602, a potent and selective EP300/CBP bromodomain inhibitor, in a Phase 1 clinical study in multiple myeloma (Press release, Opna Bio, AUG 26, 2024, View Source [SID1234646108]). The trial is expected to enroll up to 130 total patients with relapsed or refractory multiple myeloma at sites in the U.S. Multiple myeloma is a type of blood cancer derived from malignant plasma cells in the bone marrow. There are approximately 180,000 people worldwide who are diagnosed with multiple myeloma and 117,000 deaths attributable to the disease annually.

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The first patient was dosed at The START Center for Cancer Research in Grand Rapids, Michigan, with Dr. Andrew Sochacki, principal investigator, leading the study team. "OPN-6602 represents an exciting and novel therapeutic target that will provide a much-needed option for our relapsed and refractory myeloma patient population," stated Dr. Sochacki. "The innovative approach of this therapy has the potential to significantly improve outcomes for patients who have exhausted other treatment options. This collaboration with Opna underscores our commitment to advancing cutting-edge research and delivering new, effective therapies to patients who need them the most."

OPN-6602 is an oral, small molecule inhibitor of the E1A binding protein (EP300) and CREB-binding protein (CBP). Through EP300/CBP inhibition, OPN-6602 down regulates expression of IRF4 and MYC, two transcription factors that drive growth of multiple myeloma cells. Preclinical data presented at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) 2024 Annual Meeting showed that OPN-6602 significantly reduced tumor growth as a single agent (71% tumor growth inhibition) in the OPM-2 human multiple myeloma cell xenograft model as well as increased anti-tumor activity (>100% tumor growth inhibition) in combination studies.

"We are pleased to initiate clinical testing of OPN-6602, which has shown potent anti-tumor activity in multiple myeloma models as well as other cancers," said Reinaldo Diaz, MBA, chief executive officer.

The objectives of the open-label study are to assess safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of OPN-6602 as monotherapy and in combination with dexamethasone in patients with relapsed or refractory multiple myeloma. The company expects to enroll up to 90 patients in the dose-escalation cohort, with an additional 40 patients in the dose-expansion cohort. The completion date is expected in the second half of 2026.

Company Appoints Industry Experts to Board of Directors

Additionally, Opna announced the appointments of Axel Bolte, MBA, MSc, to board director and Stephanie Oestreich, PhD, MPA, to board observer, following the Myeloma Investment Fund’s recent investment in Opna. The Myeloma Investment Fund is the philanthropic investment fund of the Multiple Myeloma Research Foundation.

Mr. Bolte most recently served as founder, president and CEO of Inozyme Pharma (INZY), a rare disease company where he continues as director and advisor. He also served as a board director of IVERIC Bio (ISEE) until its sale to Astellas. Mr. Bolte is managing partner for Healthcare Advisors GmbH and was previously venture partner and investment advisor for HBM Partners AG, while serving on multiple boards of private and public companies.

Dr. Oestreich, the managing director of the Myeloma Investment Fund, brings decades of experience, previously serving as chief business officer at Galecto, vice president at Mnemo Therapeutics, as well as venture partner at RA Capital. She was also executive vice president at Evotec where she built its North American investment arm and started an incubator with Samsara BioCapital, as well as worked in business development and commercial functions at Roche and Novartis.

"We welcome Axel Bolte and Dr. Stephanie Oestreich to our board, both of whom bring valuable hands-on experience in industry operations, disease areas, financing and business development," said Diaz.