On June 12, 2023 IDEAYA Biosciences, Inc. (NASDAQ: IDYA), a precision medicine oncology company committed to the discovery and development of targeted therapeutics, reported selection of a monotherapy expansion dose for the Phase 2 clinical trial evaluating IDE397 in patients having solid tumors with MTAP deletion (Press release, Ideaya Biosciences, JUN 12, 2023, View Source [SID1234632678]).

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"We have selected a IDE397 Phase 2 monotherapy expansion dose for evaluation in our high-priority solid tumor types with MTAP deletion, including NSCLC, bladder cancer and gastroesophageal cancer. We are in the early stages of enrollment into our global Phase 2 clinical trial monotherapy expansion and have clinical objectives to further define IDE397’s monotherapy efficacy in our high priority solid tumor types and to address contribution of components for clinical combinations," said Dr. Darrin M. Beaupre, M.D., Ph.D., Chief Medical Officer, IDEAYA Biosciences.

IDE397 is a potent and selective small molecule inhibitor targeting methionine adenosyltransferase 2a (MAT2A). IDEAYA is clinically evaluating IDE397 as monotherapy in a Phase 1/2 clinical trial in patients having solid tumors with methylthioadenosine phosphorylase (MTAP) deletion, with ongoing enrollment into the global Phase 2 clinical trial.

IDEAYA is focusing monotherapy expansion cohorts in high-priority tumor types with MTAP deletion, including NSCLC, bladder cancer and gastricesophageal cancer. MTAP deletion is estimated to occur in ~16% of non-small cell lung cancer (NSCLC), ~30% of bladder cancer and ~15% to ~25% of gastricesophageal cancer. These monotherapy indications are being prioritized based on preliminary clinical efficacy and preclinical data demonstrating in vivo efficacy in relevant patient- and/or cell-derived xenograft models and observed endogenous pathway suppression in MTAP deleted tumors. These data were presented at the 2023 Annual Meeting of the American Association of Cancer Research (AACR 2023).

The company observed tumor shrinkage in multiple patients treated with IDE397 monotherapy in IDEAYA’s high-priority MTAP-deletion solid tumor types, including a pre-treated patient that had an observed partial response (PR) by RECIST 1.1 (~40% tumor reduction) at the first post-baseline scan.

IDEAYA is collaborating with Amgen to clinically evaluate IDE397 in combination with AMG 193 in patients having solid tumors with MTAP deletion. AMG 193 is the Amgen investigational MTA- cooperative protein arginine methyltransferase 5 (PRMT5) inhibitor. The clinical evaluation of IDE397 with AMG 193 represents a novel and potential first-in-class synthetic lethality combination. Targeting two mechanistically distinct nodes of the MTAP methylation pathway – MAT2A and PRMT5 provides a synergistic approach for targeting MTAP-null tumors.

In May 2023, IDEAYA reported clearance of the Amgen-sponsored Investigational New Drug (IND) application and U.S. FDA authorization to proceed with the IDE397 / AMG 193 Phase 1/2 clinical trial. The Phase 1/2 clinical trial will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of IDE397 in combination with AMG 193.

IDEAYA and Amgen co-presented preclinical data at AACR (Free AACR Whitepaper) 2023 demonstrating deep and durable anti-tumor efficacy for the IDE397 and AMG 193 combination in a NSCLC MTAP-null CDX model. These data showed complete responses following approximately 30 days of combination treatment at doses below the maximally efficacious preclinical dose for each compound, which were durable from approximately study-day 40 to study-day 100. The IDE397 and AMG 193 combination was well tolerated, with no observed body weight loss through the approximate 30 days of combination treatment in these models. Additionally, the results of gene expression analysis of hallmark pathways, alternative splicing analysis and retained intron analysis collectively demonstrated that combined pharmacological inhibition of MAT2A and PRMT5 deepens the biological response through maximal pathway suppression. The enhanced combination effect was observed selectively in MTAP-deleted models.

Pursuant to the mutually non-exclusive CTCSA, Amgen is the sponsor of the IDE397 and AMG 193 combination clinical trial and each of IDEAYA and Amgen will supply their respective compounds, IDE397 and AMG 193. Each party will pay fifty percent (50%) of the external third-party costs for conducting the clinical trial and be wholly responsible for their respective own internal costs and expenses in support of the clinical trial. The companies will jointly own clinical data and all intellectual property, if any, relating to the combined use of IDE397 and AMG 193 from the clinical trial. Each party retains commercial rights to its respective compounds, including with respect to use as a monotherapy or combination agent. The companies have formed a joint oversight committee responsible for coordinating all regulatory and other activities in support of the clinical trial.

On June 12, 2023 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) (Actinium or the Company), a leader in the development of targeted radiotherapies, reported positive SIERRA trial results in an oral presentation at the European Hematology Association (EHA) (Free EHA Whitepaper) 2023 Congress (EHA) (Free EHA Whitepaper) in Frankfurt, Germany on June 10 (Press release, Actinium Pharmaceuticals, JUN 12, 2023, View Source [SID1234632675]). The abstract included data from Actinium’s SIERRA controlled phase 3 study comparing the efficacy of Iomab-B based conditioning, a first-in-class targeted radiotherapy, versus physician’s choice of conventional care in older, relapsed/refractory acute myeloid leukemia (r/r AML) with active disease.

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"We are honored to have been accepted for an oral presentation at EHA (Free EHA Whitepaper)," said Sandesh Seth, Chairman and Chief Executive Officer. "This presentation is the third of four orals at prestigious medical conferences globally in 2023, including TCT, EBMT and SNMMI, reflecting the paradigm changing potential of Iomab-B in facilitating transplants for patients who are currently not considered for transplant."

Details of the EHA (Free EHA Whitepaper) presentation:

Presentation Title: SIERRA trial results with a targeted radiotherapy, Iomab-B, a myeloablative conditioning with reduced intensity tolerability yields high CR, long term survival in HSCT ineligible active r/r AML
Presenting Author: Dr. Boglarka Gyurkocza
Session Type/Title: Oral / SCT Clinical
Presentation ID: S248 (View Source)
Date and Time: June 10, 11:30am – 12:45pm CET

In patients over 55 with active r/r AML, Iomab-B was able to safely deliver myeloablative doses of targeted radiation to bone marrow. Iomab-B based conditioning with bone marrow transplant (BMT) resulted in rapid engraftment and high initial complete remission/complete remission with incomplete platelet recovery rates, a favorable toxicity profile and resulted in statistically significant improvement in the pre-specified primary endpoint of durable complete remission (dCR). The majority of patients who achieved dCR are long term survivors, in whom OS and EFS was significant. Iomab-B based conditioning was well-tolerated and provided access to HSCT with curative potential in a vulnerable patient population traditionally not considered eligible for HSCT.

On June 12, 2023 Mustang Bio, Inc. ("Mustang" or the "Company") (Nasdaq: MBIO), a clinical-stage biopharmaceutical company focused on translating today’s medical breakthroughs in cell and gene therapies into potential cures for difficult-to-treat cancers and rare genetic diseases, reported that updated data from the ongoing Phase 1/2 clinical trial of MB-106, a CD20-targeted, autologous CAR T cell therapy, show a favorable safety and efficacy profile in patients with Waldenstrom macroglobulinemia ("WM"), a rare form of blood cancer (Press release, Mustang Bio, JUN 12, 2023, View Source [SID1234632674]). MB-106 is being developed in a collaboration between Mustang and Fred Hutchinson Cancer Center ("Fred Hutch") to treat patients with relapsed or refractory B-cell non-Hodgkin lymphomas ("B-NHLs") and chronic lymphocytic leukemia ("CLL").

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The updated results from the single-institution Phase 1/2 clinical trial were presented during a poster session at the European Hematology Association (EHA) (Free EHA Whitepaper) 2023 Hybrid Congress ("EHA2023") by Mazyar Shadman, M.D., M.P.H., Associate Professor and physician at Fred Hutch and University of Washington.

"As we continue to evaluate MB-106 in this single-institution study, we’re encouraged by its potential to become an outpatient treatment option for WM and other B-cell malignancies, including indolent and aggressive non-Hodgkin lymphomas," said Dr. Shadman. "We have observed ongoing responses to MB-106 with improvements in the quality of response over time, along with a favorable safety profile."

All six patients in the study were previously treated with Bruton’s tyrosine kinase inhibitors ("BTKi"), and their disease continued to progress while on BTKi’s. Overall, 83% (5/6) of the patients treated with MB-106 responded to treatment, including 2 complete responses, 1 very good partial response, 1 partial response, and 1 minor response. In addition, 1 patient experienced stable disease. One of the patients who achieved a complete response has remained in remission for 22 months, with an immunoglobulin M (IgM) level that decreased rapidly to the normal range after treatment with MB-106 and has remained normal since. No patient has started additional anti-WM treatment after being treated with MB-106. From a safety perspective, cytokine release syndrome (CRS) occurred in five patients: two patients with grade 1 and three patients with grade 2. One patient experienced grade 1 immune effector cell-associated neurotoxicity syndrome (ICANS). No grade 3 or 4 CRS or grade 2, 3 or 4 ICANS has been observed.

Manuel Litchman, M.D., President and Chief Executive Officer of Mustang, commented, "MB-106 has the potential to fill a significant unmet need, as there are currently no CAR T treatments for WM approved by the U.S. Food and Drug Administration ("FDA"). The MB-106 data from the Phase 1/2 clinical trial taking place at Fred Hutch continue to be encouraging for WM and other B-NHLs. The positive data from this study and the FDA Orphan Drug Designation MB-106 received for WM support the treatment of patients with WM in the Phase 1 portion of our multicenter Phase 1/2 clinical trial which is underway and also support a fast-to-market Phase 2 strategy for this indication. We plan to report initial clinical data from the multicenter program shortly."

For more information on the clinical trials, please visit www.clinicaltrials.gov using the identifier NCT05360238 for the multicenter trial and NCT03277729 for the ongoing trial at Fred Hutch.

Scientists at Fred Hutch played a role in developing these discoveries, and Fred Hutch and certain of its scientists may benefit financially from this work in the future.

About MB-106 (CD20-targeted autologous CAR T Cell Therapy)
CD20 is a membrane-embedded surface molecule which plays a role in the differentiation of B-cells into plasma cells. The CAR T was developed by Mustang’s research collaborator, Fred Hutch, in the laboratories of the late Oliver Press, M.D., Ph.D., and Brian Till, M.D., Associate Professor in the Clinical Research Division at Fred Hutch, and was exclusively licensed to Mustang in 2017. The lentiviral vector drug substance used to transduce patients’ cells to create the MB-106 drug product produced at Fred Hutch has been optimized as a third-generation CAR derived from a fully human antibody, and MB-106 is currently in a Phase 1/2 open-label, dose-escalation trial at Fred Hutch in patients with B-NHLs and CLL. The same lentiviral vector drug substance produced at Fred Hutch is being used to transduce patients’ cells to create the MB-106 drug product produced at Mustang Bio’s Worcester, MA, cell processing facility for administration in the multicenter Phase 1/2 clinical trial that is now open to enrollment under Mustang Bio’s IND. It should be noted that Mustang Bio has introduced minor improvements to its cell processing to facilitate eventual commercial launch of the product. In addition, prior to commercial launch, Mustang Bio will replace the Fred Hutch lentiviral vector drug substance with vector produced at a commercial manufacturer. Additional information on the trials can be found at View Source using the identifier NCT05360238 for the multicenter trial and NCT03277729 for the ongoing trial at Fred Hutch. Mustang Bio has entered into an Asset Purchase Agreement pursuant to which it has agreed to sell, subject to the satisfaction of certain conditions, its leasehold interest in its cell processing facility and expects to enter into a manufacturing services agreement with the prospective purchaser to provide for the continued production of the MB-106 drug product. For additional information, please refer to the Current Report on Form 8-K filed by Mustang Bio with the U.S. Securities and Exchange Commission ("SEC") on May 22, 2023.

On June 12, 2023 Theratechnologies Inc. ("Theratechnologies" or the "Company") (TSX: TH) (NASDAQ: THTX), a biopharmaceutical company focused on the development and commercialization of innovative therapies, reported that it will hold a video conference call on Tuesday, June 13, 2023, to update investors and analysts on the Phase 1 trial of its lead peptide-drug conjugate (PDC) candidate, sudocetaxel zendusortide (formerly TH1902), for the treatment of solid tumors (Press release, Theratechnologies, JUN 12, 2023, View Source [SID1234632671]).

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During the call, Theratechnologies will provide insights on preliminary Phase 1 safety and efficacy data that were presented at the 2023 annual meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), as well as the U.S. Food and Drug Administration’s (FDA) recent agreement to the Company’s amended Phase 1 trial protocol. Both events are significant milestones in the development of sudocetaxel zendusortide, a PDC that targets the sortilin (SORT1) receptor, and a product of Theratechnologies’ SORT1+ Technology platform.

Paul Lévesque, President and Chief Executive Officer of Theratechnologies, will host the call, which will feature presentations from the Company’s Senior Vice President and Chief Medical Officer, Christian Marsolais, Ph.D., as well as from investigators from the Phase 1 trial. Presenters will be available to answer questions following prepared remarks.

Registration information:

Title: Oncology Investigator Call for Investors & Analysts: Phase 1 Trial Update
Date: June 13, 2023
Time: 10:00 AM EDT
Webcast link: View Source
Dial in: 1-888-317-6003 (toll free) or 1-412-317-6061 (International)
(Participant entry #: 2792560)
An archived webcast will also be available on the Company’s Investor Relations website under ‘Past Events’.

About SORT1+ Technology and Sudocetaxel Zendusortide (TH1902)
Theratechnologies has established its SORT1+ Technology platform as an engine for the development of proprietary peptide-drug conjugates (PDCs) that target the sortilin (SORT1) receptor, which is expressed in multiple tumor types. SORT1 is a "scavenger" receptor that plays a significant role in protein internalization, sorting, and trafficking. Expression of SORT1 is associated with aggressive disease, poor prognosis, and decreased survival. It is estimated that SORT1 is expressed in 40% to 90% of endometrial, ovarian, colorectal, triple-negative breast (TNBC), and pancreatic cancers, making this receptor an attractive target for anticancer drug development.

Sudocetaxel zendusortide is a first-of-its-kind SORT1-targeting PDC, and the first compound to emerge from the SORT1+ Technology platform. A new chemical entity, sudocetaxel zendusortide employs a cleavable linker to conjugate (attach) a proprietary peptide to docetaxel, a well-established cytotoxic chemotherapeutic agent used to treat many cancers. The FDA granted Fast Track designation to sudocetaxel zendusortide as a single agent for the treatment of all sortilin-positive recurrent advanced solid tumors that are refractory to standard therapy. Sudocetaxel zendusortide is currently being evaluated in a Phase 1 clinical trial.

On June 12, 2023 TriSalus Life Sciences Inc., (TriSalus or the Company), an oncology company in the process of going public through a business combination transaction (the Business Combination) with MedTech Acquisition Corporation (Nasdaq: MTAC) (MedTech or MTAC), reported additional Phase 1 clinical data presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2023 Annual Meeting taking place in Chicago, Illinois, from June 2-6, 2023 (Press release, TriSalus Life Sciences, JUN 12, 2023, View Source [SID1234632669]).

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TriSalus’ ongoing Phase 1 Pressure-Enabled Regional Immuno-Oncology (PERIO-01) (NCT04935229) clinical study for uveal melanoma with liver metastases (UMLM) is studying an investigational class C toll-like receptor-9 agonist, SD-101, delivered intravascularly by TriSalus’ TriNav Infusion System (TriNav) using the Company’s proprietary Pressure-Enabled Drug Delivery (PEDD) method of administration. PERIO-01 is evaluating whether this platform approach can improve the performance of systemic checkpoint inhibitors in patients with UMLM.

"The data presented by Dr. Kamaneh Montazeri from Mass General Brigham at ASCO (Free ASCO Whitepaper) reflect important clinical progress of our Phase 1 PERIO-01 trial and builds on the promising data released in April," said Steven C. Katz, MD, FACS, Chief Medical Officer at TriSalus. "We are pleased that SD-101 in combination with systemic checkpoint inhibition and delivered with TriNav was well tolerated based on a low treatment related serious adverse event rate of 5% and resulted in immune cell activation and natural killer cell expansion. We look forward to moving into Phase 2 later this year and are optimistic about the potential of SD-101 playing an important role in the management of patients with UMLM."

Pharmacokinetic data indicate that the strategy of delivering a toll-like receptor-9 agonist with the PEDD method results in high drug levels in the liver, while the drug is undetectable after four hours in the serum in 97% of patients with available data. The immune effects in liver metastases and the blood are consistent with broad tumor microenvironment modulation and the ability of SD-101 to deplete myeloid derived suppressor cells (MDSCs) in the liver.

PERIO-01 is an open-label, first-in-human Phase 1 trial of SD-101, administered by hepatic arterial infusion with TriNav using PEDD in UMLM. The study consists of dose-escalation cohorts of SD-101 (2, 4, or 8 mg) alone or with immune checkpoint inhibition. At the data cutoff as of May 12, 2023, 39 patients were enrolled in the PERIO-01 trial, with each having received at least one dose of SD-101. Of the patients with available data, five patients were treatment-naïve and 81% had failed at least one prior line of therapy, including three patients on their sixth-line of treatment.

Following receipt of SD-101, patients demonstrated a statistically significant expansion of peripheral natural killer cells, along with evidence of decreased expression of exhaustion markers on these cells. Increases in serum cytokines, including IFNg and IL-18, also supported systemic immune activation. Additionally, decreased levels of ctDNA levels were observed within eight out of 13 evaluable patients. Stable disease was noted as the best on-treatment response for target lesions in 15 out of 25 patients, with one partial response.

These findings, along with reductions of intratumoral MDSCs and decreases in ARG-1 (arginase 1) and IDO-1 (indoleamine 2,3-dioxygenase-1) gene levels, support the hypothesis that SD-101 delivered via PEDD may have favorable immune effects within the liver and systemically.

Overall, the data emerging from the PERIO-01 trial continues to indicate immunologic changes are occurring within the liver, with decreases in ctDNA and disease control observed across a group of heavily pre-treated patients with UMLM, as well as a low treatment-related serious adverse event rate.

The data were also selected for presentation at the Developmental Therapeutics – Immunotherapy Poster Discussion Session on June 3, 2023 at 3:00pm CT.