On September 18, 2023 PharmAbcine Inc. (KOSDAQ: 208340ks), a clinical-stage biotech company focusing on the development of next-generation antibody therapeutics, reported that the Company has received approval from the HREC (Human Research Ethics Committee) in Australia for the Phase 1a/b trial (MarkV-01 Trial) of PMC-309, an anti-VISTA (V-domain Ig Suppressor of T cell Activation) antibody candidate (Press release, PharmAbcine, SEP 18, 2023, View Source;bmode=view&idx=16374112&t=board [SID1234649178]).

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The MarkV-01 trial is a first-in-human, open-label Phase 1a/b study which will proceed in two parts, the first part with PMC-309 monotherapy followed by the second part in combination with KEYTRUDA (pembrolizumab), MSD (Merck & Co., Inc., Rahway, NJ., USA)’s anti-PD-1 therapy. PharmAbcine already announced in December 2022 that the Company signed a clinical collaboration agreement with MSD, under which MSD would supply KEYTRUDA for the combination cohort.

The primary objective of the study is to evaluate the safety, tolerability, and determine the recommended RP2D (Recommended Phase 2 dose) in both parts. The second objective is to evaluate PK profile (pharmacokinetics) and clinical efficacy, including ORR (overall response rate), DCR (disease control rate), and PFS (progression-free survival).

PMC-309 is a novel anti-VISTA antagonizing antibody that can be used for the treatment of various tumor types. It inhibits VISTA, an immune checkpoint receptor mainly expressed on MDSCs (Myeloid-Derived Suppressor Cells) and Tregs (regulatory T cells). By inhibiting the VISTA pathway on immunosuppressive cells, PMC-309 can promote anti-tumor effects by indirectly activating T cells unlike the existing immuno-oncology drugs that directly target and activate T cells. This unique mode of action allows PMC-309 to play a pivotal role in regulating the VISTA-expressing immunosuppressive cells found abundantly in tumor microenvironment.

The antibody already demonstrated in nonclinical studies that it can promote both innate immunity (monocyte activation, M1 macrophage proliferation) and adaptive immunity (T cell activation) unlike the existing drugs, which show notable changes only in adaptive immunity. In addition, the in vivo data showed significantly improved tumor growth inhibition when PMC-309 is used in combination with an anti-PD-1 drug compared to both monotherapies of PMC-309 and an anti-PD-1 drug.

"The approval of our clinical trial for the anti-VISTA antibody marks a significant milestone for PharmAbcine, bringing us one step closer to providing a groundbreaking treatment option for patients with unmet medical needs in the field of immuno-oncology," commented Dr. Jin-San Yoo, CEO of PharmAbcine. "We are very excited to begin this trial and looking forward to evaluating PMC-309’s safety and efficacy across multiple tumor types in both mono and combo therapy."

Dr. Yoo also added, "We are grateful for the collaborative work with MSD and would like to thank everyone, including the regulatory, our colleagues, partners, shareholders, and investors, who has contributed to making this achievement possible."

For more information about the MarkV-01 trial, visit clinicaltrials.gov and search for the reference identifier NCT05957081.

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

About PMC-309

PMC-309 is a novel IgG1 anti-VISTA antagonizing antibody that can be used for the treatment of various tumor types. By inhibiting VISTA, an immune checkpoint receptor mainly expressed on MDSC and Tregs, it can play a pivotal role in maintaining the immunosuppressive environment around the tumor cells.

In the nonclinical studies, it has been demonstrated that PMC-309 can promote both innate immunity (monocyte activation, M1 macrophage proliferation) and adaptive immunity (T cell activation) unlike the existing drugs which show significant changes only in adaptive immunity. In addition, the in vivo data showed that PMC-309 significantly improved tumor growth inhibition when used in combination with an anti-PD-1 drug compared to both monotherapies of PMC-309 and an anti-PD-1 drug. These findings suggest that PMC-309 can offer a new treatment strategy in immuno-oncology area as it can be used in combination with other drugs to improve their low-response rates.

About MarkV-01 Trial

The MarkV-01 trial is a Phase 1a/b, first-in-human (FIH), open label study to evaluate the safety, tolerability, and PK of PMC-309, a mAb against the human VISTA ligand, in participants with advanced or metastatic solid tumors administered as a monotherapy and in combination with pembrolizumab. The primary objective of the study is to evaluate the safety, tolerability, and determine recommended RP2D in both parts. The second objective is to evaluate PK profile and clinical efficacy, including ORR, DCR, and PFS.

Phase 1a is a 2-part dose escalation; both parts will adopt the modified toxicity probability interval (mTPI) design with a dose limiting toxicity (DLT) rate of 30% for dose finding.

Part A is planned as a PMC-309 dose escalation.
Part B is planned as a PMC-309 dose escalation in combination with pembrolizumab.
Phase 1b is planned as a cohort expansion with PMC-309 administered as a monotherapy (Cohort A) at the preliminary RP2D found at Phase 1a (Part A) and in combination with pembrolizumab (Cohort B) with PMC-309 at the maximum tolerated dose (MTD)/preliminary RP2D found at Phase 1a (Part B).

A minimum of 67 participants are to be enrolled to the study.

On September 18, 2023 Osmol Therapeutics, a privately held biopharmaceutical company focused on developing a treatment to prevent chemotherapy-induced peripheral neuropathy (CIPN), reported that the U.S. Food and Drug Administration (FDA) notified the company that the first-in-human clinical trial of OSM-0205 in healthy subjects for the prevention of CIPN may proceed (Press release, Osmol Therapeutics, SEP 18, 2023, View Source [SID1234637886]). Osmol filed the Investigational New Drug application (IND) with the FDA for OSM-0205 in August 2023.

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Microtubule-based chemotherapy treatments, which destroy cancer cells based on microtubule disruption, produces an intracellular calcium surge that damages neurons, leading to CIPN. Each year, approximately 360,000 cancer patients in the U.S. and E.U. are treated with taxanes most commonly for the treatment of breast cancer but also for prostate cancer as well as other malignant solid tumors. Approximately 80% of breast cancer patients experience some degree of CIPN. Currently there are no FDA-approved treatments for CIPN, and the only way to mitigate the effect of this painful and often debilitating condition is by interrupting treatment or reducing the dosage of chemotherapy, which can adversely impact patient outcomes.

"Preventing CIPN would address a major women’s health issue for which there are currently no FDA-approved disease modifying treatment options," said Arthur DeCillis, MD, Chief Medical Officer, Osmol Therapeutics. "OSM-0205 is administered intravenously immediately prior to chemotherapy treatment and has the potential to protect neurons in patients by preventing the surge in intracellular calcium associated with CIPN. This first-in-human Phase 1 clinical trial in healthy subjects will determine the safety, tolerability, and pharmacokinetics of single ascending doses of OSM-0205 intravenous infusion to select a dose to evaluate in Phase 2 clinical studies in breast cancer patients."

About OSM-0205

Osmol’s lead drug, OSM-0205, is based on Dr. Barbara Ehrlich’s research in neuronal calcium sensor-1 (NCS1) at Yale School of Medicine and is designed to prevent the off-target calcium surge caused by taxanes and potentially other chemotherapy treatments associated with peripheral nerve damage. Data from preclinical studies conducted by Osmol show that pre-treatment with OSM-0205 prevents the pathologic damage caused by these chemotherapy agents.

On September 18, 2023 Cellectar Biosciences, Inc., a late-stage clinical biopharmaceutical company focused on the discovery, development and commercialization of targeted drugs for the treatment of cancer, reported that the European Medicines Agency (EMA) has granted Priority Medicines (PRIME) designation to iopofosine I 131, the company’s lead small-molecule drug candidate, for Waldenstrom’s macroglobulinemia (WM) in patients who have received two or more prior treatment regimens (Press release, Cellectar Biosciences, SEP 18, 2023, View Source [SID1234637602]).

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The PRIME program aims to optimize development plans and speed up evaluation of medicines that may offer a major therapeutic advantage over existing treatments or benefit patients without treatment options. These medicines are considered priority medicines by the EMA and are intended to reach patients earlier. To be accepted for PRIME, new therapies must demonstrate the potential to significantly address an unmet medical need in clinical trials.

"PRIME designation from the EMA further underscores our confidence in iopofosine I 131 to provide a differentiated and highly needed new treatment option for patients with WM," said James Caruso, president and CEO of Cellectar. "We expect to release top-line data from the CLOVER-WaM pivotal trial in the fourth quarter of 2023 and submit our NDA in March, 2024. With PRIME designation now in hand we look forward to advancing our EU strategy to bring this potential targeted treatment option to patients in the US and EU as quickly as possible."

The U.S. Food and Drug Administration (FDA) has granted Cellectar’s lead asset iopofosine I 131, a small-molecule Phospholipid Drug Conjugate (PDC) designed to provide targeted delivery of iodine-131 (radioisotope), Fast Track Designation for WM patients having received two or more prior treatment regimens, as well as relapsed (or refractory) multiple myeloma and relapsed (or refractory) diffuse large B-cell lymphoma (DLBCL). The company expects to complete our ongoing Phase 2b WM pivotal trial (NCT02952508) in the second half of 2023 and assuming an FDA Priority Review and approval, remains on target for a 2024 US product launch.

On September 18, 2023 Vividion Therapeutics, Inc. (Vividion), reported that it has initiated dosing of patients in a Phase I oncology clinical trial of its investigational oral Kelch-like ECH Associated Protein 1 (KEAP1) activator, VVD-130037 (Press release, Bayer, SEP 18, 2023, View Source [SID1234635305]). Vividion is a biopharmaceutical company utilizing novel discovery technologies to unlock high value, traditionally undruggable targets with precision therapeutics for devastating cancers and immune disorders, and a wholly owned and independently operated subsidiary of Bayer AG. The start of the trial represents a major milestone for Vividion’s innovative chemoproteomics platform.

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"The initiation and dosing of this clinical trial marks a major inflection point for Vividion as we advance to a clinical stage company. We are proud of the progress we have made in a relatively short amount of time with our novel pipeline of previously undruggable protein targets for prominent oncology and immunology diseases," said Aleksandra Rizo M.D., Ph.D., Chief Executive Officer of Vividion. "We are energized by the future, as we work to deliver multiple programs to the clinic starting in 2023."

"We are leveraging Vividion’s innovative chemoproteomics technology to develop new therapies with the potential to stop or reverse the progression of diseases," said Christian Rommel, Ph.D., Member of the Executive Committee of Bayer’s Pharmaceuticals Division and Head of Research and Development. "For millions of patients and their families, cancer continues to be a devastating disease, and new treatments are needed to address key drivers of tumor cell survival and growth. The start of Vividion’s first clinical trial takes us a step closer to a potentially meaningful new oncology treatment for various forms of cancer."

Vividion’s proprietary chemoproteomic approach, which allows the company to unlock high value, traditionally undruggable target biology with precision therapeutics for cancers and immune disorders, has been thriving following the company’s acquisition by Bayer in August 2021. The transaction allows Vividion to operate at arm’s length in a best-of-both-worlds’ model, preserving its innovative, entrepreneurial culture while also leveraging Bayer’s deep expertise in small molecule development, global capabilities and financial strength.

"We are excited to announce the initiation and dosing of Vividion’s first drug in clinical development from our chemoproteomic platform," said Jenna Goldberg, M.D., Chief Medical Officer of Vividion. "This is a first-in-class clinical candidate, aimed to target cancers with activation of the KEAP1-NRF2 pathway. This would be a novel opportunity in cancer treatment."

The company is advancing multiple novel biology programs toward the clinic and has more than a dozen similar pipeline opportunities emerging in early discovery in the fields of oncology and immunology. The Phase I clinical trial will evaluate the safety, pharmacokinetics and pharmacodynamics and preliminary efficacy of VVD-130037 in patients with advanced solid tumors. Trial participants will have a histologically confirmed metastatic or unresectable solid tumor. Participants will receive ascending doses of VVD-130037, orally, once daily in 21-day treatment cycles.

On September 18, 2023 NH TherAguix ("NHT"), a research-based biotech company specialized in the development of innovative nanomedicines for the treatment of cancer by radiotherapy, and Jean PERRIN Cancer Center in Clermont-Ferrand reported the completion of phase I recruitment and the entry into Phase II for the Nano-GBM phase I/II trial in newly diagnosed glioblastoma, sponsored by Jean PERRIN Cancer Center and led by Pr Julian Biau, radiation oncologist.

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This phase I/II clinical trial investigates the tolerance and efficacy of the combination of AGuIX intravenous injections with radiotherapy plus concomitant temozolomide in the treatment of newly diagnosed glioblastoma.

Nano-GBM is a multicentric, randomized, open-label and non-comparative Phase I/II trial. The aim of the dose escalation phase I was to determine the recommended dose of experimental drug to be evaluated for the phase II. 3 dose levels of AGuIX (50mg/kg, 75mg/kg and 100mg/kg) have been tested on eight patients treated in Phase I. These patients with unresected or partially resected glioblastoma have received four injections of AGuIX in combination with temozolomide (75 mg/m²/day) and radiotherapy (60 Gy in 30 fractions of 2 Gy), followed by adjuvant temozolomide according to Stupp protocol, as the standard of care. AGuIX injections were well-tolerated. In addition, MRI analysis has confirmed that AGuIX nanoparticles selectively accumulated in glioblastoma. The Data Safety Monitoring Board, an independent group of experts external to the trial, has confirmed the safety profile of AGuIX in combination with chemo-radiotherapy for the treatment of glioblastoma patients, has validated the recommended dose chosen as well as the continuation of the trial into Phase II.

Pr. Julian Biau stated: "We are happy to have successfully completed the phase I at Jean PERRIN Cancer Center. Based on a favorable safety profile of AGuIX in combination with Stupp protocol, we are encouraged to pursue assessment of this nanoparticle efficacy within the phase II of this innovative clinical trial, in collaboration with other investigator centers".

Dr. Olivier de Beaumont, CMO of NHT said: "After first hints of efficacy in brain metastases indication, NHT is pursuing further the clinical assessment of AGuIX in neuro-oncology. Based on a robust scientific package demonstrating efficacy of AGuIX in rodents with glioblastoma, this phase I/II clinical trial was designed with the objective to demonstrate the safety and efficacy of AGuIX in patients with glioblastoma de novo. With the completion of the phase I of the Nano-GBM study, we are confirming the good tolerance of AGuIX administered at 100mg/kg via intravenous infusions and we are extremely proud to enter the phase II randomized part of the study with the objective to show a patient clinical benefit in combination with Stupp protocol as standard of care".

This phase II study will be randomized with two arms: an experimental arm in which patients will be treated with AGuIX at a dose of 100 mg/kg in combination with radio-chemotherapy (40 patients), and a control arm in which patients will be treated with radio-chemotherapy alone (20 patients). To date, the two first patients of the phase II have been included in the control arm.

The primary endpoint of this phase II study is progression-free survival at 6 months. Secondary endpoints include AGuIX distribution in tumors, progression-free survival, overall survival, overall objective response rate and the safety profile of AGuIX in combination with radiotherapy and temozolomide.