On March 9, 2022 FogPharma, a biopharmaceutical company pioneering a new class of precision medicines that could ultimately prove applicable to all therapeutic targets, including those previously considered "undruggable," reported the selection of its lead product development candidate, FOG-001, a first-and-only-in-class direct β-catenin inhibitor (Press release, FogPharma, MAR 9, 2022, View Source [SID1234609820]). FOG-001 represents the first of FogPharma’s proprietary, conformationally hyperstabilized α-helical polypeptides (Helicon polypeptides), a new class of therapeutics designed to combine the targeting strength and specificity of antibodies with the broad tissue distribution, intracellular target engagement and oral dosing optionality of small molecules.

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Dysregulation of the Wnt/β-catenin signaling pathway has been shown to occur in at least 20% of all human cancers. In biochemical and cellular studies, FOG-001 has been shown to potently, precisely and selectively disrupt the interaction of β-catenin with its obligate transcription factor, TCF. Preclinical studies have demonstrated the ability of FOG-001 to cause tumor growth inhibition and regression by disrupting β-catenin-dependent signaling. FOG-001, the inaugural member of FogPharma’s TCF-Catenix family of direct-acting β-catenin antagonists, combines key features that distinguish it from previously reported Wnt/β-catenin pathway modulators: FOG-001 acts inside the cell, where it directly binds the key oncogenic driver β-catenin; and FOG-001 blocks TCF-β-catenin engagement at the most downstream node in the canonical Wnt pathway, thus abrogating the signal transmission mechanism by which most, if not all, known Wnt pathway mutations are believed to drive oncogenesis.

"The selection of FOG-001 as our development candidate, within two and a half years of initiating the discovery of a TCF-Catenix drug for a target widely considered "undruggable," underscores the rapid progress being made at FogPharma as we seek to advance medicine by a quantum leap. We are rapidly achieving mastery in the rapid deployment of a new therapeutic modality designed to surmount the challenges of intractable disease-driving targets," said Gregory Verdine, Ph.D., founder and chief executive officer of FogPharma. "Genetic evidence has long implicated β-catenin as being a principal driver of human cancer, but this target had been frustratingly beyond therapeutic reach, until the discovery of FOG-001. We look forward to advancing our first Helicon drug candidate, FOG-001, into clinical development, with the overarching aim of providing a fundamentally new and potentially significant treatment option for the large number of cancer patients whose disease is driven by derangement of the Wnt pathway."

FogPharma plans to file an investigational new drug (IND) application with the U.S. Food and Drug Administration (FDA) for FOG-001 and initiate clinical development by mid-2023.

About FogPharma’s Universal Druggability Platform
FogPharma’s Helicon peptide drug discovery engine integrates directed evolution, proprietary α-helix conformational hyperstabilization chemistry, highly multiplexed drug optimization technology, artificial intelligence including deep learning and machine learning, structure-based drug discovery, and multiscale manufacturing to rapidly discover Helicon polypeptide therapeutics against important, previously intractable targets with broad applicability to virtually all disease areas.

On March 9, 2022 Guardant Health, Inc. (Nasdaq: GH), a leading precision oncology company, reported it will present new data from its broad portfolio of blood tests at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting from April 8-13, 2022 (Press release, Guardant Health, MAR 9, 2022, View Source [SID1234609819]). Included in the presentation will be data from its multi-cancer screening assay, next-generation Guardant SHIELD.

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"We are excited to share the feasibility data for our innovative multi-cancer screening assay. This data will demonstrate that our assay provides sensitive detection of early-stage cancers with accurate tissue of origin identification," said AmirAli Talasaz, Guardant Health co-CEO. "The data to be presented at this year’s AACR (Free AACR Whitepaper) meeting demonstrates our deep commitment to providing physicians with the resources to help patients at all stages of cancer live longer and healthier lives."

Full List of Guardant Health Presentations

Development of a highly-sensitive targeted cell-free DNA epigenomic assay for early-stage multi-cancer screening (Abstract 2141). Session MS.CL11.02 – Biomarkers 2, oral presentation.
CDK4/6 inhibitors (CDK4/6i) is effective in the real-world setting for hormone receptor-positive metastatic breast cancer (HR+ MBC) with ESR1 mutations and fusions (Abstract 5248)
Multiomic, plasma-only circulating tumor DNA (ctDNA) assay identifies breast cancer patients with minimal residual disease (MRD) and predicts distant recurrence (Abstract 3403/9)
Genomic landscape of circulating tumor DNA alterations in patients with paraganglioma and pheochromocytoma (Abstract 5790)
Predictive ability of circulating tumor DNA by Guardant360 in poziotinib-treated patients with NSCLC harboring HER2 exon 20 insertion mutations (Abstract 3400/6)
Longitudinal evaluation of ctDNA molecular response for monitoring clinical benefit and investigating treatment related impacts in metastatic colorectal cancer patients treated with different drug regimens (Abstract 5748)
Occurrence of BRAF class II and III alterations is common across solid tumors and is associated with inferior clinical outcomes in NSCLC and melanoma (Abstract 4122/6)
Characterization of sub-clonal RAS/BRAF alterations in an anti-EGFR treated advanced CRC cohort using a liquid biopsy-based real world clinical genomics database (Abstract 5245)

On March 9, 2022 NorthStar Medical Radioisotopes, LLC, a global innovator in the development, production and commercialization of radiopharmaceuticals used for therapeutic applications and medical imaging, and Convergent Therapeutics, Inc., a clinical stage radiopharmaceutical company, reported the signing of a long-term supply agreement for the therapeutic medical radioisotope, actinium-225 (Ac-225) (Press release, NorthStar Medical Radiostopes, MAR 9, 2022, View Source [SID1234609818]). Under terms of the agreement, NorthStar will provide Convergent with its environmentally preferred, high purity non-carrier-added (n.c.a.) Ac-225. Convergent will use NorthStar’s Ac-225 to radiolabel its lead asset, CONV01-α, a prostate-specific membrane antigen (PSMA)-targeted monoclonal antibody, currently being investigated as a potential ground-breaking treatment for prostate cancer.

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Ac-225 is a high energy alpha-emitting radioisotope of increasing interest for clinical studies investigating the use of targeted radiopharmaceutical therapy (RPT), which combines select molecules with therapeutic radioisotopes, such as Ac-225, to directly target and deliver therapeutic doses of radiation to destroy cancer cells in patients with serious disease. Ac-225 carries sufficient radiation to cause cell death in a localized area of targeted cells, while its half-life limits unwanted radioactivity in patients. Clinical research and commercial use of Ac-225 are severely constrained by chronic short supply due to limitations of current production technology. NorthStar is positioned to be the first commercial-scale producer of Ac-225 for advancing clinical research and commercial radiopharmaceutical products. The Company will use its environmentally-sound electron accelerator technology to produce n.c.a. Ac-225 that is free of long-lived radioactive contaminants and byproducts associated with other production methods, which pose regulatory and waste management challenges for hospitals and health systems.

"NorthStar is applying the same development expertise to rapidly advance large-scale production of n.c.a. Ac-225 that has positioned us at the forefront of U.S. radioisotope production as the only commercialized producer of the important medical radioisotope molybdenum-99 (Mo-99)," said Stephen Merrick, President and Chief Executive Officer of NorthStar Medical Radioisotopes. "Like all NorthStar processes, our n.c.a. Ac-225 production technology is environmentally sustainable and non-uranium based, utilizing state-of-the-art electron beam accelerator production that provides increased capacity and scheduling flexibility. Facility design is complete and we expect construction to be underway soon on our dedicated Actinium-225 Production facility, with initial production of radiochemical grade Ac-225 planned for late 2023, and a Drug Master File to be submitted to the FDA in 2024, which, upon acceptance by the FDA, will allow NorthStar to provide cGMP grade Ac-225. We are very pleased to enter this Ac-225 supply agreement with Convergent Therapeutics, and we look forward to working with them moving forward. Our companies share a vision of developing and delivering innovative technology to drive research and ensure clinical availability of targeted radiopharmaceutical therapies for patients with cancer."

"Convergent has demonstrated that dual targeting of surface cancer molecules, like prostate-specific membrane antigen (PSMA), improves antitumor efficacy and may represent a truly disruptive and advantageous therapeutic option to treat prostate cancer," said Philip Kantoff, M.D., Chief Executive Officer of Convergent Therapeutics. "Our lead candidate, CONV01-α, is a monoclonal antibody radiolabeled with Ac-225, and is specifically designed to bind to PSMA, which is highly expressed in most prostate cancer. Once bound, CONV01-α becomes internalized, enabling delivery of supra-additive therapeutic doses of radiation directly into prostate cancer cells. The power of labeling CONV01-α with an alpha-emitting radioisotope such as Ac-225 is in its ability to maximize antitumor impact while minimizing radiation to adjacent tissue. NorthStar is our ideal partner for Ac-225 supply based on their leadership experience and commercial expertise in cutting-edge, accelerator-based radioisotope production technology. We look forward to working with NorthStar to supply Ac-225 for our clinical studies and future commercialization needs as we seek to deliver highly transformative treatments for patients with prostate and other cancers."

On March 9, 2022 Enzychem Lifesciences (KOSDAQ: 183490), a late-stage biotechnology company, announced today that the company has completed the final Clinical Study Report (CSR) for their Phase 2 study of EC-18 in Chemoradiation-induced Oral Mucositis (CRIOM), entitled "Phase 2, multi-center, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of EC-18 in altering the severity and course of oral mucositis (OM) in subjects being treated with concomitant chemoradiation therapy for cancers of the mouth, oropharynx, hypopharynx, and nasopharynx (Press release, Enzychem Lifesciences, MAR 9, 2022, View Source [SID1234609817])."

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The phase 2 U.S. study was designed as 2 stages with 105 randomized subjects at 21 sites to evaluate the safety, tolerability, and efficacy of its lead compound, EC-18 on mitigating severe oral mucositis (SOM) in head and neck subjects receiving concomitant chemoradiation therapy for cancers of the mouth, oropharynx, hypopharynx, and nasopharynx.

An iDSMB evaluated the safety endpoint every two weeks in a blinded fashion, until 30 days after the last dosing of Stage 1. If a safety issue was noted, the iDSMB was instructed to unblind the treatment assignments to ascertain if the adverse event (AE) was associated with the study drug. Since no safety issues were identified at the end of Stage 1, Stage 2 commenced using 2000 mg of the study drug, consistent with a positive safety outcome.

The primary efficacy endpoint demonstrated that the median duration of SOM (defined as WHO Grades 3 or 4) from baseline through short-term follow-up period (STFU) was 0.0 days in the EC-18 group versus 13.5 days in the placebo group (100% reduction).

The secondary efficacy endpoints showed that the incidence of SOM from baseline through the active treatment period was reduced by 37.1% in the EC-18 group when compared to the placebo group (40.9% vs. 65.0%). Similarly, the incidence of SOM from baseline through the STFU period also reported a reduction by 35.0% in comparison to the placebo group (45.5% vs. 70.0%). Based on the estimated median time to onset of SOM with a confidence interval of 95% utilizing the Kaplan Meier analysis, the time of onset of SOM was 8 days longer in the EC-18 group in comparison to the placebo group (43 days vs. 51 days). Also, EC-18 showed a median delay of 11.5 days in time to the first use of opioid analgesics when compared to the placebo group (37 days vs. 25.5 days).

On March 9, 2022 ITM Isotope Technologies Munich SE (ITM), a leading radiopharmaceutical biotech company, reported the presentation of the design for its second phase III trial, COMPOSE (NCT04919226) at the 19th Annual European Neuroendocrine Tumor Society (ENETS) Conference being held in a hybrid format in Barcelona on March 10-11, 2022 (Press release, ITM Isotopen Technologien Munchen, MAR 9, 2022, View Source [SID1234609816]). The study is designed to evaluate the efficacy and safety of ITM’s lead radiopharmaceutical candidate, ITM-11 (n.c.a. 177Lu-edotreotide), compared to best standard of care for patients with well‐differentiated high grade 2 and grade 3 somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (G2+G3 SSTR+ GEP-NETs). ITM-11 is a Targeted Radionuclide Therapy consisting of the high-quality radioisotope, no-carrier-added lutetium-177 (n.c.a. 177Lu) combined with the somatostatin analogue edotreotide. The poster presentation follows the recent announcement of the first patient treated in the pivotal study.

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"ITM is demonstrating its commitment to patients with neuroendocrine tumors expanding its clinical program through the COMPOSE trial with the aim of broadening therapeutic options for patients with high grade GEP-NETs. The potential role of ITM-11 in this area will enable a more personalized approach beyond chemotherapy," said Jorge Hernando, MD, PhD, Medical Oncologist, Vall d´Hebron Institute of Oncology (VHIO), Barcelona, Spain and investigator for COMPOSE. "I am honored to be presenting ITM´s study design here in Barcelona at this year’s ENETS, the most important conference in the neuroendocrine tumors field in Europe – especially now, after two years of online meetings due to COVID-19."

"Our aspiration with COMPOSE is to demonstrate the value of ITM-11 in more advanced GEP-NET patient populations, as we strive to provide them with better treatment options," stated Steffen Schuster, CEO of ITM. "We value the opportunity to present our second phase III trial to the expert ENETS community as we continue advancing our lead candidate through the clinic."

COMPOSE is an international, prospective, randomized, controlled, open-label, multi-center phase III study to evaluate the efficacy, safety, and patient-reported outcomes of first or second-line treatment with ITM-11 compared to best standard of care in patients with well-differentiated high grade 2 and grade 3 (Ki-67 index 15-55), SSTR+, GEP-NETs. The study aims to randomize 202 patients 1:1 to ITM-11 or best standard of care — either chemotherapy (CAPTEM or FOLFOX) or everolimus — according to the investigator’s choice. The primary endpoint of the study is progression-free survival (PFS), which will be assessed every 12 weeks from randomization onwards. Secondary outcome measures include overall survival (OS) up to two years after disease progression. COMPOSE builds upon ITM’s first ongoing phase III clinical trial, COMPETE (NCT03049189), examining patients with grade 1 and grade 2, GEP-NETs. ITM’s subsidiary, ITM Solucin GmbH is the sponsor of both studies.

Presentation information

Title: COMPOSE: Phase III Trial of 177Lu-edotreotide versus Standard of Care in Well-differentiated (WD) Aggressive Grade 2 and Grade 3 Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs)

Abstract No: #3389

Poster No: M03

Session: Phase III Clinical Trials in Progress

Presenter: Jorge Hernando, MD, PhD, Vall d’Hebron University Hospital, Barcelona, Spain

About Targeted Radionuclide Therapy

Targeted Radionuclide Therapy is an emerging class of cancer therapeutics, which seeks to deliver radiation directly to the tumor while minimizing radiation exposure to normal tissue. Targeted radiopharmaceuticals are created by linking a therapeutic radioisotope to a targeting molecule (e.g., peptide, antibody, small molecule) that can precisely recognize tumor cells and bind to tumor-specific characteristics, like receptors on the tumor cell surface. As a result, the radioisotope accumulates at the tumor site and decays, releasing a small amount of ionizing radiation, thereby destroying tumor tissue. The highly precise localization enables targeted treatment with minimal impact to healthy surrounding tissue.

About ITM-11 (n.c.a. 177Lu-edotreotide)

ITM-11, ITM’s therapeutic radiopharmaceutical candidate being investigated in the phase III clinical studies COMPETE and COMPOSE, consists of two components: the medical radioisotope no-carrier-added lutetium-177 (n.c.a. 177Lu) and the targeting molecule edotreotide, a synthetic form of the peptide hormone somatostatin that targets neuroendocrine tumor-specific receptors. Edotreotide binds to these receptors and places the medical radioisotope n.c.a. lutetium-177 directly onto the diseased neuroendocrine cells so that it accumulates at the tumor site. N.c.a. lutetium-177 is internalized into the tumor cells and decays, releasing medical radiation (ionizing β-radiation) with a maximum radius of 1.7 mm and destroying tumor tissue.