On August 11, 2022 VerImmune, Inc. ("VerImmune"), a biotechnology company developing new oncology therapeutic modalities that redirect the body’s pre-existing immunity toward cancer, reported that it has been accepted into the fully sponsored Assay Cascade characterization and testing program conducted by the Nanotechnology Characterization Laboratory (NCL) at the National Cancer Institute’s, part of the National Institutes of Health, Frederick National Laboratory for Cancer Research (Press release, VerImmune, AUG 11, 2022, View Source [SID1234618120]).

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Nanomedicines accepted into the NCL Assay Cascade program undergo a rigorous evaluation that may include sterility and endotoxin testing, physicochemical characterization, in vitro hemato- and immunotoxicity, and in vivo studies to evaluate safety, efficacy, and pharmacokinetics. The studies are tailored to each individual nanomedicine and are designed to promote the clinical translation of these novel therapies. All studies are funded by the NCI and conducted free of charge for Awardees.

"We are excited to be accepted into this highly competitive program sponsored by the National Cancer Institute" said John Troyer, COO of VerImmune Inc and Principal Investigator. "Acceptance into this program is an important step in validating our strategy since NCL accepts proposals with strong clinical potential. We look forward to this collaboration which will strengthen our existing manufacturing data for FDA submissions."

On August 11, 2022 Promontory Therapeutics Inc., a clinical stage pharmaceutical company focused on oncology therapeutics, reported the peer-reviewed publication of mechanistic studies with lead candidate PT-112 in this month’s issue of Cancers (volume 14, issue 16), an MDPI publication (Press release, Promontory Therapeutics, AUG 11, 2022, View Source [SID1234618119]). The in vitro study, entitled "PT-112 induces mitochondrial stress and immunogenic cell death, targeting tumor cells with mitochondrial deficiencies," showed that PT-112 was selective to cells with defective mitochondria, inducing cancer cell death through non-conventional mechanisms, including increased mitochondrial stress, free radical generation, and immunogenic cell death (ICD), a form of cell death that is reliant upon cellular stresses, and elicits an immune response.

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PT-112, under phase 1/2 clinical development, has shown clinical activity against advanced pretreated solid tumors and has been shown to induce robust ICD. This manuscript reports PT-112’s anti-cancer activity, including mitochondrial stress and selectivity to cancer metabolic processes, specifically mitochondrial dysfunction.

Key findings include:

Mouse tumor cells presenting mitochondrial DNA mutations and the resulting glycolytic phenotype were more sensitive to cell death induced by PT-112 compared to cells with an intact oxidative phosphorylation (OXPHOS) pathway

PT-112 induced mitochondrial stress and initiated autophagy, which is associated with an integrated stress response and with subsequent ICD

PT-112 caused calreticulin exposure, further substantiating PT-112’s ICD effects

HIF-1α expression was higher in cells sensitive to PT-112

Such selectivity of PT-112 has the potential for clinical applications in metabolically aggressive cancers

"Our study published in Cancers provides evidence of PT-112-induced cancer cell organelle stresses, and their relationship to ICD," said Matthew Price, Executive VP & COO of Promontory Therapeutics. "These findings are part of ongoing efforts crossing several research collaborations to define the causes of PT-112’s known immunogenic effects, and are supportive of the uniqueness of its mechanism of action."

The full results are available in the journal Cancers 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) 2018 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. The Phase 1 study in patients with relapsed or refractory multiple myeloma presented at ASH (Free ASH Whitepaper) is the third completed Phase 1 study of PT-112. Monotherapy Phase 2 development is ongoing in mCRPC, and now includes the Phase 2 proof of concept study in thymic epithelial tumors under the company’s formal collaboration with the NCI. The PD-L1 combination Phase 2a study is ongoing in a dose confirmation cohort of non-small cell lung cancer (NSCLC) patients.

On August 11, 2022 Greenwich LifeSciences, Inc. (Nasdaq: GLSI) (the "Company"), a clinical-stage biopharmaceutical company focused on the development of GLSI-100, an immunotherapy to prevent breast cancer recurrences in patients who have previously undergone surgery, reported the following (Press release, Greenwich LifeSciences, AUG 11, 2022, View Source [SID1234618118]):

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Phase III clinical trial, Flamingo-01, has officially started
Multiple sites have begun the screening and enrolling process
Flamingo-01 is evaluating the safety and efficacy of GLSI-100 (GP2 + GM-CSF) in HER2/neu positive breast cancer patients who had residual disease or high-risk pathologic complete response at surgery
CEO Snehal Patel commented, "We are thrilled to begin what we hope will be a successful reproduction of our Phase IIb trial, in which GLSI-100 safely prevented metastatic breast cancer recurrences with 100% disease free survival. The hard work and effort of the GLSI team and our partners have led us to this major milestone. We look forward to sharing more site contact information with patients and their clinicians in the future as we activate more sites and some of the largest oncology networks in the US and Europe, making Flamingo-01 available to as many patients as possible."

The commencement of the Phase III trial transitions the Company into pre-commercialization activities, which include:

Working with the FDA in preparation for a BLA submission and commercial launch
Implementing a global strategy for launching GP2 in international markets outside the US and Europe
Initiating large scale manufacturing, packaging, and marketing
The Company anticipates the following additional activities/milestones:

Phase III clinical trial progress and open label data will be presented at major conferences
Licensing discussions may accelerate as the interim analysis approaches
Other assets may be developed by acquisition or internal research, including T cell therapies that may be discovered in the Phase III trial by studying GP2’s robust immunogenicity
Additional patents for GP2 based on the Phase III trial findings, manufacturing, and pharmacy procedures are planned to be filed to extend patent life
For Patients Seeking to Participate in Flamingo-01

Patients who are interested in participating in the Flamingo-01 Phase III clinical trial can contact the Company by email at [email protected] and can obtain clinical site contact information to contact sites directly on www.clinicaltrials.gov with identifier NCT05232916 (view here).

About Flamingo-01 and GLSI-100

Flamingo-01 (NCT05232916) is a Phase III clinical trial designed to evaluate the safety and efficacy of GLSI-100 (GP2 + GM-CSF) in HER2/neu positive breast cancer patients who had residual disease or high-risk pathologic complete response at surgery and who have completed both neoadjuvant and postoperative adjuvant trastuzumab based treatment. The trial will be led by Baylor College of Medicine and will include US and international clinical sites from university-based hospitals and cooperative networks. In the double-blinded arms of the Phase III trial, approximately 500 HLA-A*02 patients will be randomized to GLSI-100 or placebo, and up to 100 patients of other HLA types will be treated with GLSI-100 in a third arm. The trial has been designed to detect a hazard ratio of 0.3 in invasive breast cancer-free survival, where 28 events will be required. An interim analysis for superiority and futility will be conducted when at least half of those events, 14, have occurred. This sample size provides 80% power if the annual rate of events in placebo-treated subjects is 2.4% or greater.

About Breast Cancer and HER2/neu Positivity

One in eight U.S. women will develop invasive breast cancer over her lifetime, with approximately 282,000 new breast cancer patients and 3.8 million breast cancer survivors in 2021. HER2/neu (human epidermal growth factor receptor 2) protein is a cell surface receptor protein that is expressed in a variety of common cancers, including in 75% of breast cancers at low (1+), intermediate (2+), and high (3+ or over-expressor) levels.

On August 11, 2022 F-star Therapeutics, Inc. (NASDAQ: FSTX) ("F-star" or the "Company"), a clinical-stage biopharmaceutical company pioneering bispecifics in immunotherapy so more people with cancer can live longer and improved lives, reported second quarter 2022 financial results and corporate highlights (Press release, F-star, AUG 11, 2022, View Source [SID1234618117]).

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"During the second quarter, we steadfastly remained focused on advancing our four clinical programs," said Eliot Forster, CEO of F-star Therapeutics, Inc., "We continued the enrollment for the FS118 study in PD-1 acquired resistance head and neck cancer patients and have cleared the initial futility hurdle. The dose-escalation study for FS222 continues to progress well, and we are happy to report that therapy remains well-tolerated and clinically active at pharmacologically active dose levels, including in patients with low levels of PD-L1 expression. We also initiated the combination study of FS120 with KEYTRUDA in patients with advanced cancers and we look forward to evaluating the potential clinical benefits of the combined therapies. Dose escalation of SB 11285 continues. Both the monotherapy and combination with atezolizumab remain well tolerated."

Second Quarter 2022 and Recent Highlights:

F-star planned acquisition by invoX Pharma: As previously disclosed, on June 22, 2022, the Company entered into a definitive agreement to be acquired by invoX Pharma Limited, a wholly owned subsidiary of Sino Biopharmaceutical Limited (HKEX 11771.HK), for $7.12 per share for an approximate total equity value of $161 million in cash. Subject to the satisfaction of customary closing conditions, including regulatory approvals, the transaction is expected to close in the second half of 2022.
License Agreement with Takeda to develop and commercialize a novel next-generation immuno-oncology bispecific antibody therapeutic: Under the terms of the agreement, F-star will grant Takeda a worldwide, exclusive royalty-bearing license to research, develop, and commercialize a bispecific antibody against an immuno-oncology target using F-star’s proprietary Fcab and mAb2 platforms. Takeda will be responsible for all research, development, and commercialization activities under the agreement.
FS118 in acquired resistance head and neck Phase 2 interim update: FS118 appeared to be well tolerated in line with Phase 1 results and has cleared the pre-determined futility hurdle for the initial stage of the head and neck acquired resistance cancer trial. We believe that we are on track to achieve the predefined efficacy levels and are pleased to be observing long-term clinical benefit for patients. The enrollment of the patients for the remainder of the study continues well, paving the way for combination therapy in this hard-to-treat patient population.
FS222 Phase 1 clinical trial update: The monotherapy dose-escalation progresses well. FS222 has demonstrated emerging clinical antitumor activity with a tolerability profile typical of checkpoint inhibitors and elicits dose-dependent increases in soluble CD137 and PD-L1 levels, indicative of target engagement and increases in immune cell activation and proliferation.
FS120 Initiation of KEYTRUDA combination dosing: Pharmacologically active dose levels have been reached and we have initiated dose escalation of FS120 in combination with Keytruda.
FS118 poster presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2022 Annual Meeting demonstrating a novel LAG-3 reduction and shedding mechanism: Data revealed that the unique tetravalent structure of FS118 plays a critical role in evoking LAG-3 shedding, and cell surface reduction, in tumor-infiltrating lymphocytes (TILs), enabling FS118 to overcome compensatory upregulation of LAG-3 induced by PD-(L)1 blockade.
Second Quarter 2022 Financial Summary:

Cash Position
Cash and cash equivalents were $53.0 million as of June 30, 2022, compared to $78.5 million at December 31, 2021.

R&D Expense
R&D expenses were $8.7 million for the quarter ended June 30, 2022, compared to $8.3 million for the corresponding quarter in 2021. The $0.4 million increase is primarily due to an increase of $2.9 million in clinical trial costs, $0.9 million of R&D consulting, staff and other R&D costs, offset by the UK R&D tax credit of $3.4 million, which is treated as a reduction in expense.

G&A Expense
G&A expenses were $7.5 million for the quarter ended June 30, 2022, compared to $6.5 million for the second quarter 2021. This $1.0 million increase is primarily due to $2.5 million in transaction related costs, offset by reductions of $1.0 million of non-transaction related legal and professional fees, $0.4 million in stock-based compensation expense and $0.1 million in other G&A expense.

Net Loss Attributable to Common Shareholders
Net loss was $19.0 million or a loss per share of $0.88 (basic and diluted) for the quarter ended June 30, 2022, as compared to a net loss of $15.5 million or a loss per share of $0.91 (basic and diluted) for the quarter ended June 30, 2021.

Conference Call and Webcast:

F-star will not be hosting a conference call to discuss Q2 2022 financial results or corporate update in light of the pending transaction with invoX Pharma announced on June 23, 2022.

On August 11, 2022 Panbela Therapeutics, Inc. (Nasdaq: PBLA), a clinical stage company developing disruptive therapeutics for the treatment of patients with urgent unmet medical needs, reported it has enrolled the first patient in its global clinical trial to study SBP-101 in combination with Gemcitabine and Nab-Paclitaxel in patients with metastatic pancreatic ductal adenocarcinoma, which is referred to as the ASPIRE trial, a randomized double-blind placebo-controlled trial, with a primary endpoint of overall survival (Press release, Panbela Therapeutics, AUG 11, 2022, View Source [SID1234618116]). Detailed information on the trial can be located at View Source

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"While site initiation was gradual, we are pleased with the current momentum of the ASPIRE trial. We expect that a significant number of global sites will be open by year-end with the full complement of sites open by the first quarter 2023. Australia opened last week with the first site activated within the country, and now they’ve enrolled the first patient into the study," commented, Jennifer K. Simpson, PhD, MSN, CRNP, President & Chief Executive Officer of Panbela. "Australian study centers have been wonderful to work with and were important contributors to our phase 1 trial, enrolling a heavy preponderance of the 50 patients. We’re excited to reach this milestone of first patient enrolled, as we move forward towards interim analysis which is expected to complete in early 2024."

Australia marked the second country activated for the ASPIRE trial, and first to enroll, with approximately 90 additional sites expected to be activated across 10 countries by early 2023.

Additionally, in response to European and FDA regulatory feedback, the study was amended to include the total trial sample size (600 subjects) and the design modified to utilize overall survival as the primary endpoint to be examined at an interim analysis. While the trial is expected to take approximately 36 months to fully enroll, the interim analysis is still expected to occur in early 2024.

About our Pipeline

The pipeline consists of assets currently in clinical trials with an initial focus on familial adenomatous polyposis (FAP), first-line metastatic pancreatic cancer, neoadjuvant pancreatic cancer, colorectal cancer prevention and ovarian cancer. The combined development programs have a steady cadence of catalysts with programs ranging from pre-clinical to registration studies.

SBP-101

SBP-101 is a proprietary polyamine analogue designed to induce polyamine metabolic inhibition (PMI) by exploiting an observed high affinity of the compound for pancreatic ductal adenocarcinoma and other tumors. The molecule has shown signals of tumor growth inhibition in clinical studies of US and Australian metastatic pancreatic cancer patients, demonstrating a median overall survival (OS) of 14.6 months which is final, and an objective response rate (ORR) of 48%, both exceeding what is seen typically with the standard of care of gemcitabine + nab-paclitaxel suggesting potential complementary activity with the existing FDA-approved standard chemotherapy regimen. In data evaluated from clinical studies to date, SBP-101 has not shown exacerbation of bone marrow suppression and peripheral neuropathy, which can be chemotherapy-related adverse events. Serious visual adverse events have been evaluated and patients with a history of retinopathy or at risk of retinal detachment will be excluded from future SBP-101 studies. The safety data and PMI profile observed in the current Panbela sponsored clinical trial provides support for continued evaluation of SBP-101 in a randomized clinical trial. For more information, please visit View Source .

Flynpovi

Flynpovi is a combination of CPP-1X (eflornithine) and sulindac with a dual mechanism inhibiting polyamine synthesis and increase polyamine export and catabolism. In a Phase 3 clinical trial in patients with sporadic large bowel polyps, the combination prevented > 90% subsequent pre-cancerous sporadic adenomas versus placebo. Focusing on FAP patients with lower gastrointestinal tract anatomy in the recent Phase 3 trial comparing Flynpovi to single agent eflornithine and single agent sulindac, FAP patients with lower GI anatomy (patients with an intact colon, retained rectum or surgical pouch), Flynpovi showed statistically significant benefit compared to both single agents (p≤0.02) in delaying surgical events in the lower GI for up to four years. The safety profile for Flynpovi did not significantly differ from the single agents and supports the continued evaluation of Flynpovi for FAP.

CPP-1X

CPP-1X (eflornithine) is being developed as a single agent tablet or high dose power sachet for several indications including prevention of gastric cancer, treatment of neuroblastoma and recent onset Type 1 diabetes. Preclinical studies as well as Phase 1 or Phase 2 investigator-initiated trials suggest that CPP-1X treatment is well tolerated and has potential activity.