On June 8, 2022 Promontory Therapeutics Inc., a clinical stage pharmaceutical company focused on oncology therapeutics, reported the peer-reviewed publication of its first-in-human Phase 1 study of lead therapeutic candidate, PT-112 in the July 2022 issue of eClinicalMedicine, part of The Lancet’s Discovery Science (Press release, Promontory Therapeutics, JUN 8, 2022, View Source [SID1234615787]). The study, entitled "Phase I Study of PT-112, a novel Pyrophosphate-Platinum Immunogenic Cell Death Inducer, in Advanced Solid Tumours," showed that PT-112 was safe and well-tolerated in heavily pre-treated patients with advanced cancers, and demonstrated prolonged responses against thymoma and lung cancers, along with radiographic and serum marker improvement in prostate cancer.

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PT-112 has been validated as an immunogenic cell death inducer in pre-clinical models, and is under active Phase 2 clinical development. In the first-in-human dose escalation study PT-112 was given as monotherapy to eligible patients with progressing, advanced solid tumors via intravenous infusion on days 1, 8, 15 of a 28-day cycle in a 3+3 dose-escalation trial. The primary endpoint was to assess safety and pharmacokinetics, and to identify a recommended Phase 2 dose. The secondary objective was exploratory assessment of anti-tumor activity.

Study findings from 66 heavily pre-treated patients treated across 11 dose levels of PT-112 (12-420 mg/m2) include:

The recommended phase 2 dose was determined to be 360 mg/m2
The most common treatment-related adverse events included fatigue (35%), nausea (24%), and peripheral neuropathy (21%)
Treatment-related Grade 3 adverse events were experienced by 27% of patients, with no grade 4-5 events observed.
Durable, confirmed RECIST partial responses were induced in non-small cell lung cancer, small cell lung cancer, and thymoma, some of which persisted for prolonged periods even after treatment discontinuation. Two additional unconfirmed RECIST responses were observed.
Radiographic and serum marker reductions were observed among ten patients with metastatic castration resistant prostate cancer, four of whom survived two years or longer
"We are pleased to publish the results of our first Phase 1 study of PT-112 in The Lancet’s eClinicalMedicine," said Matthew Price, Executive VP & COO of Promontory Therapeutics. "The evidence supports our belief that PT-112’s immunogenic cell death induction makes it a promising future treatment option in several possible cancer indications, and that its foundational safety allows us to consider numerous ways to deploy it. The experience we gained in this study underlies the direction taken by the company in our current Phase 2 studies of PT-112."

The study is registered under NCT02266745 and the full dose-escalation results are available in eClinicalMedicine and online here.

About PT-112
PT-112 is the first small-molecule conjugate of pyrophosphate in oncology, and possesses a unique pleiotropic mechanism of action that promotes immunogenic cell death (ICD) through the release of damage associated molecular patterns (DAMPs) that bind to dendritic cells and lead to downstream immune effector cell recruitment in the tumor microenvironment. PT-112 represents a highly potent inducer of this immunological form of cancer cell death. Further, PT-112 harbors a property known as osteotropism, or the propensity of the drug to reach its highest concentrations in certain areas of the bone, making it a candidate for treatment of patients with cancers that originate in, or metastasize to, the bone. The first in-human study of PT-112 demonstrated an attractive safety profile and evidence of long-lasting responses among heavily pre-treated patients and won "Best Poster" within the Developmental Therapeutics category at the ESMO (Free ESMO Whitepaper) Annual Congress. The combination Phase 1b dose escalation study of PT-112 with PD-L1 checkpoint inhibitor avelumab in solid tumors was reported in an oral presentation at the ESMO (Free ESMO Whitepaper) 2020 Virtual Congress. A Phase 1 study in patients with relapsed or refractory multiple myeloma was presented at ASH (Free ASH Whitepaper) 2020. Monotherapy Phase 2 development is ongoing in mCRPC, and in a Phase 2 proof of concept study in thymic epithelial tumors under the company’s formal collaboration with the National Cancer Institute (NCI).

On June 8, 2022 Bristol Myers Squibb (NYSE:BMY) reported that it will announce results for the second quarter of 2022 on Wednesday, July 27, 2022. Company executives will review financial results and address inquiries from investors and analysts during a conference call at 8:00 a.m. ET on the same date (Press release, Bristol-Myers Squibb, JUN 8, 2022, View Source [SID1234615756]).

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Investors and the general public are invited to listen to a live webcast of the call at View Source." target="_blank" title="View Source." rel="nofollow">View Source To be directly connected to the conference call, enter your information here; the link will be active 15 minutes prior to the scheduled start time of the call, and does not require a dial-in number or operator assistance to be connected. Investors and the public can also access the live webcast by dialing in the U.S. toll free 888-300-0211 or international +1 786-460-7199, confirmation code: 6873379. Materials related to the call will be available at View Source prior to the start of the conference call.

A replay of the webcast will be available on View Source approximately three hours after the conference call concludes. A replay of the conference call will be available beginning at 11:30 a.m. EDT on July 27 through 11:30 a.m. EDT on August 10, 2022, by dialing in the U.S. toll free 888-203-1112 or international +1 719-457-0820, confirmation code: 6873379.

On June 8, 2022 Provectus (OTCQB: PVCT) reported that updated data from the Company’s initial expansion cohort of patients with uveal melanoma metastatic to the liver (mUM) in its cancers-of-the-liver Phase 1 trial of investigational immunocatalyst PV-10 (rose bengal sodium) (NCT00986661) were presented at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting, held June 3-7 in Chicago, Illinois and online (Press release, Provectus Biopharmaceuticals, JUN 8, 2022, View Source [SID1234615772]).

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Twenty-nine percent (29%) of Stage IV M1a mUM patients achieved mCR and were alive from 12.4+ to 48.8+ months after starting PV-10 treatment. All M1a patients had hepatic metastases injected with PV-10; 50% had extrahepatic disease, which was not injected with PV-10. A portion of M1a patients underwent positron emission tomography (PET)-computed tomography (CT) (PET-CT) cancer imaging, which previously has not been widely recognized as an important tool for monitoring tumor response in mUM because historical treatments essentially did not produce mCRs.

This ongoing single-center mUM study at MD Anderson Cancer Center (MDACC) in Houston, Texas has been led since inception by Sapna Patel, MD, Associate Professor, Department of Melanoma Medical Oncology, Division of Cancer Medicine at MDACC. Up to three hepatic mUM tumors can be injected per PV-10 treatment cycle. Response assessments are performed at Day 28, and then every three months. Patients with additional, injectable, visceral hepatic mUM disease may receive additional cycles of PV-10 after Day 28. Eligible patients may also receive standard of care immune checkpoint blockade (CB; i.e., either PD-1 or combination CTLA-4 + PD-1) during and after PV-10 treatment.

Highlights from the ASCO (Free ASCO Whitepaper) presentation, with data supplementation

PV-10 can induce mCR in injected/adscopal and non-injected/abscopal lesions.
mCR suggests immunogenic cell death in mUM patients with non-injected liver metastases.
RECIST response assessment may underestimate the effect of PV-10 in injected tumors. 2D EASL is more sensitive than RECIST to changes in injected lesions. PET-CT is more sensitive than either RECIST or 2D EASL.
Translational research is underway at MDACC and Moffitt Cancer Center to elucidate the molecular basis for mCR responders vs non-responders.
A copy of the ASCO (Free ASCO Whitepaper) poster presentation is available on Provectus’ website at: View Source

Ed Pershing, Chair of Provectus’ Board of Directors (Board), said, "We could not be more grateful to these study patients, their families and caregivers, the MD Anderson Cancer Center clinical trial team, and the ocular melanoma patient advocacy community for the opportunity to better develop a comprehensive approach for identifying, surveilling, treating, and hopefully defeating this terrible disease in its early metastatic stage. We have gained valuable insights from this clinical trial that will be considered for future patient assessment and treatment protocols, as we continue to advance PV-10 for the treatment of metastatic uveal melanoma."

Dominic Rodrigues, Vice Chair of the Board, added, "These clinical trial data show that, while PV-10 can contribute to treatment efficacy across all disease stages, PV-10 may have much greater impact on early-stage metastatic uveal melanoma. It is important to note that patients do not typically present with M1a, M1b, or M1c disease, and that staging of study participants is based on the status of their metastatic disease course at the start of PV-10 treatment. The outcome in M1a patients who achieved a metabolic complete response implies that early intervention can be critical, and that surveillance techniques like PET imaging can play an essential role in identifying metastatic status and assessing treatment response."

Mr. Rodrigues concluded, "Metastatic uveal melanoma can be particularly threatening once it takes hold at metastatic sites around the body. These study data give us a level of confidence that the potential exists to provide a survival benefit to patients with metastatic disease by leveraging standard of care immunotherapy in combination with PV-10, and to finalize the development of a PV-10-led approach that could offer durable responses in patients by proactively integrating assessment and treatment methodologies earlier and not waiting for a patient’s disease to get out of control."

On June 8, 2022 Alpha Tau Medical Ltd. (Nasdaq: DRTS and DRTSW), ("Alpha Tau" or the "Company"), the developer of the innovative alpha-radiation cancer therapy Alpha DaRT, reported that the U.S. Food and Drug Administration (FDA) has conditionally approved the Company’s Investigational Device Exemption (IDE) application to initiate its multi-center pivotal study for the treatment of recurrent cutaneous Squamous Cell Carcinoma (SCC) using the Alpha DaRT (Press release, Alpha Tau Medical, JUN 8, 2022, View Source [SID1234615788]).

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The clinical study, entitled "A Prospective Multicenter, Pivotal, Single Arm, Open Label Clinical Study to Assess the Efficacy and Safety of Intratumoral Alpha DaRT for the Treatment of Patients with Recurrent Cutaneous Squamous Cell Carcinoma" has been approved to enroll up to 86 U.S. patients at up to 20 institutions in the U.S., in addition to any sites that may be added outside the U.S., and will focus on patients with recurrent cutaneous SCC who have failed at least first line standard of care therapy and are not indicated for another curative standard of care therapy.

"We are very excited about the upcoming commencement of our U.S. pivotal study, undoubtedly our most significant clinical trial to date," commented Alpha Tau CEO Uzi Sofer. "Our receipt of FDA conditional approval of our IDE submission is a critical milestone on our journey to bringing this exciting new therapy to patients in the U.S. and around the world"

Dr. Robert B. Den, Alpha Tau Chief Medical Officer, added, "We are thrilled to have received FDA conditional approval of our IDE, after tremendous focus on the U.S. over the past year, including successful completion of our pilot study and the upcoming initiation of this pivotal study under the FDA’s Breakthrough Device Designation Program. We have seen tremendous engagement and excitement from dozens of leading institutions in the U.S. and around the world, keen to be part of this study, and look forward to working with them on this clinical study."

Yaniv Sagie, Alpha Tau VP Quality and Regulatory Affairs, noted, "This amazing milestone represents the culmination of Alpha Tau’s rigorous teamwork and unwavering commitment to quality and regulatory excellence."

On June 8, 2022 Owkin reported that it has entered into a multi-year, strategic collaboration with Bristol Myers Squibb to apply Owkin’s Artificial Intelligence (AI) capabilities to design potentially more precise and efficient clinical trials for Bristol Myers Squibb (Press release, Owkin, JUN 8, 2022, View Source [SID1234615821]). The collaboration will initially focus on cardiovascular diseases, and has the potential to extend into projects in other therapeutic areas.

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As part of the collaboration, data from a wide network of academic medical centers and state-of-the-art machine learning techniques will be employed to enhance clinical trial design and execution with AI-powered approaches that optimize endpoint definitions, patient subgroups, and treatment effect estimation with covariate adjustment and external control arms. This new collaboration follows years of collaboration between Owkin and Bristol Myers Squibb, including a number of successful projects to identify biomarkers and improve clinical trial outcomes with covariate adjustment, using real world data.

Under the terms of the agreements, Owkin will receive $80 million in aggregate for the upfront payment and the Series B-1 equity investment by Bristol Myers Squibb and potentially further payments in excess of $100 million contingent on the collaboration achieving certain success-based milestones in conjunction with Regulatory processes.

Owkin will use the equity investment to support its ambitious data generation strategy in multiple therapeutic areas with a strong focus on multimodal and rich biological data, including the most advanced spatial single-cell omics technologies.

Gilles Wainrib, Co-founder and Chief Scientific Officer at Owkin, said:

Our collaboration will see cutting-edge machine learning methods used to maximize opportunities for patients to benefit from the latest treatments as quickly and safely as possible.

We are excited to start this collaboration with Bristol Myers Squibb, a global leader in cardiovascular with a strong development pipeline which has the potential to change the lives of millions of patients.

Our collaboration could prove transformational for patient outcomes and scientific progress, making machine learning solutions an integral part of the clinical trial process.