On December 5, 2024 Monte Rosa Therapeutics, Inc. (Nasdaq: GLUE), a clinical-stage biotechnology company developing novel molecular glue degrader (MGD)-based medicines, reported an update from its ongoing Phase 1/2 open-label, multicenter study of MRT-2359 in patients with MYC-driven solid tumors (Press release, Monte Rosa Therapeutics, DEC 5, 2024, View Source [SID1234648825]). MRT-2359 is an investigational, orally bioavailable, GSPT1-directed MGD discovered and developed by Monte Rosa Therapeutics.

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"These latest interim results from our ongoing Phase 1/2 study of MRT-2359 continue to indicate a favorable safety profile, and degradation of GSPT1 to desired levels in patients with heavily pretreated, solid tumors, including those that express high levels of MYC. Importantly, we believe the MRT-2359 safety profile supports further clinical development, with no signs of hypotension, cytokine release syndrome (CRS), or clinically significant hypocalcemia observed at any dose level and regimen, all of which have been reported as safety limitations of other GSPT1 degraders. We’re pleased to confirm the selection of 0.5 mg daily at a 21 days on, 7 days off drug dosing schedule as our recommended Phase 2 dose, a schedule that enables dosing of MRT-2359 more than twice as frequently per cycle as compared to the 5 days on, 9 days off regimen previously explored in our study and that we also believe to be more patient compliance-friendly," said Markus Warmuth, M.D., Chief Executive Officer of Monte Rosa Therapeutics. "Trial enrollment has been strong and we are working towards completing the biomarker and activity assessment of our monotherapy dose escalation study using the 21 days on, 7 days off schedule, including backfill cohorts. We have started safety assessments of MRT-2359 in combination with enzalutamide in previously treated metastatic prostate cancer patients as well as with fulvestrant in previously treated metastatic estrogen receptor-positive breast cancer patients. We look forward to providing an update on clinical data from the study as well as plans for potential expansion cohorts in the first quarter of next year."

Summary of Interim Data on Enrollment, Safety & Pharmacodynamics

Enrollment Highlights

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Patients have been dosed with MRT-2359 in 6 dose levels across two dosing schedules, namely a 5 days on, 9 days off drug (5/9) dosing schedule and a 21 days on, 7 days off drug (21/7) dosing schedule.
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The study has enrolled patients with a diverse set of tumor types, including non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), neuroendocrine (NE) tumors of the prostate, bladder and other organs of origin, androgen receptor-positive prostate cancer, and estrogen receptor-positive breast cancer.

Safety Highlights

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Using the 5/9 dosing schedule, doses of 0.5 mg and 1 mg per day were identified as having a generally favorable safety profile, while doses of 1.5 mg or higher were above the maximum tolerated dose (MTD) with thrombocytopenia being a dose limiting toxicity (DLT).
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Using the 21/7 schedule, both 0.5 and 0.75 mg were identified as having a generally favorable safety profile.
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0.5 mg using the 21/7 dose schedule was selected as the recommended phase 2 dose (RP2D) for any expansion cohorts of the Phase 1/2 study.
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Safety assessments of MRT-2359 in combination with enzalutamide in previously treated metastatic prostate cancer as well as with fulvestrant in previously treated metastatic estrogen receptor- positive breast cancer have been initiated.

Pharmacodynamic Highlights

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Pharmacodynamic effects were assessed utilizing mass spectrometry measurements of GSPT1 protein levels from paired tumor biopsies. The target levels of approximately 60% GSPT1 degradation were observed in tumor biopsies across all dose levels in relevant tumor types, supporting that the dose of 0.5 mg per day provides optimal degradation consistent with its designed activity based on preclinical studies.

Monte Rosa continues to collect and evaluate clinical results from the MRT-2359 Phase 1/2 study and expects to share updated data, including biomarker and activity data, in Q1 2025.

About MRT-2359

MRT-2359 is a potent, highly selective, and orally bioavailable investigational molecular glue degrader (MGD) that induces the interaction between the E3 ubiquitin ligase component cereblon and the translation termination factor GSPT1, leading to the targeted degradation of GSPT1 protein. The MYC transcription factors (c‑MYC, L-MYC and N-MYC) are well-established drivers of human cancers that maintain high levels of protein translation, which is critical for uncontrolled cell proliferation and tumor growth. Preclinical studies have shown this addiction to MYC-induced protein translation creates a dependency on GSPT1. By inducing degradation of GSPT1, MRT-2359 is designed to exploit this vulnerability, disrupting the protein synthesis machinery, leading to anti-tumor activity in MYC-driven tumors.

On December 5, 2024 FORE Biotherapeutics reported that the Company will participate in the Wells Fargo Virtual Private Biotech Symposium on Thursday, December 12 (Press release, Fore Biotherapeutics, DEC 5, 2024, View Source [SID1234648824]).

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William Hinshaw, Chief Executive Officer and Michael Byrnes, Chief Financial Officer, will host and participate in one-on-one meetings. Please contact Argot Partners to schedule one-on-one meetings with the management team.

On December 5, 2024 Ariceum Therapeutics (Ariceum), a private biotech company developing radiopharmaceutical products for the diagnosis and treatment of certain hard-to-treat cancers, and Eckert & Ziegler, one of the world’s largest providers of isotopes for medical, scientific and industrial use, reported the signing of a global supply agreement for the medical radionuclides Actinium-225 (Ac-225) and Lutetium-177 (Lu-177) (Press release, Ariceum Therapeutics, DEC 5, 2024, View Source [SID1234648823]).

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Following limited global availability, alongside increasing demand for Ac-225, which comes with intricate manufacturing complexities, this collaboration is a significant step forward in accelerating Ariceum’s novel targeted radiopharmaceutical pipeline programs.

Under the terms of the agreement, Eckert & Ziegler will supply Ariceum with the required quantities of non-carrier-added (n.c.a.) Ac-225 and Lu-177. Both radionuclides will be used to radiolabel Ariceum’s proprietary lead radiopharmaceutical drug (SS0110) satoreotide targeting hard-to-treat cancers in clinical studies and subsequent commercial phases. The agreement also includes options for expansion to other drugs as well as the use of additional radionuclides in preparation for future commercialisation activities.

Manfred Rüdiger, Chief Executive Officer of Ariceum Therapeutics, said: "This important global supply agreement with Eckert & Ziegler for n.c.a. Ac-225 and Lu-177 will ensure an adequate supply of radionuclide isotopes to conduct our clinical trials. We are looking forward to working with the Eckert & Ziegler team to build a robust supply chain and to reliably deliver targeted theranostic treatments for patients with hard-to-treat cancers. Our lead radiopharmaceutical drug, satoreotide is a first-in-class, antagonist of the somatostatin receptor 2 (SSTR2) labelled with Ac-225 to enter clinical development in small cell lung cancer and in Merkel Cell Carcinoma very soon."

Dr. Harald Hasselmann, Chief Executive Officer of Eckert & Ziegler, commented: "In collaborating with Ariceum, we support their mission to develop innovative radiopharmaceuticals for the benefit of patients. Both the production start for Ac-225, announced earlier this week, and the successful European approval of Theralugand, show that our goal is to sustainably reduce the shortage of high-quality radioisotopes. We aim to foster the progress of novel treatments in clinical trials and beyond, and thus contribute to saving lives."

On December 6, 2024 Treovir, Inc. reported the opening of a Phase 2 trial testing G207, an oncolytic HSV immunotherapy, in pediatric brain tumor patients (Press release, Treovir, DEC 4, 2024, View Source [SID1234648855]).

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G207 is being evaluated for efficacy in a single-arm Phase 2 study of 30 pediatric patients with high grade gliomas at first recurrence, a uniformly fatal form of pediatric brain tumors with no currently approved therapies. The Phase 2 trial will evaluate efficacy (overall survival) and confirm safety of G207, an oncolytic HSV virus. The trial is being conducted in collaboration with the Pediatric Brain Tumor Consortium, a National Cancer Institute (NCI)-supported consortium comprising 15 pediatric cancer centers, and is currently enrolling patients at Memorial Sloan Kettering Cancer Center and The University of Texas MD Anderson Cancer Center. NCI is part of the National Institutes of Health. Treovir anticipates that additional US and Canadian sites will open for enrollment in late 2024 and 2025. ClinicalTrials.gov ID NCT04482933; PBTC 061 www.pbtc.org

"With the opening of the Phase 2 study Treovir expects to expand on the positive data obtained from the Phase 1 study in pediatric patients completed in 2021" stated Michael Christini, CEO of Treovir. "There are no approved therapies for pediatric glioma and we anticipate that Phase 2 data will ultimately be used in support of a BLA filing for market approval of G207 offering a treatment option for patients in this critically underserved therapeutic area."

On December 4, 2024 TME Pharma N.V. (Euronext Growth Paris: ALTME), a clinical-stage biotechnology company focused on developing novel therapies for treatment of cancer by targeting the tumor microenvironment (TME), reported its intention to launch a €2.6 million financing to be carried out through a public offer without preferential subscription rights for in total 52,000,000 new shares (Press release, TME Pharma, DEC 4, 2024, View Source [SID1234648819]). The public offer will be reserved for the company’s shareholders only, determined as at the record date of December 10, 20241. Such shareholders can subscribe during the priority period running from December 12 to December 18, 2024 (inclusive), on a pro rata basis. Any shares not taken up by existing shareholders in the priority period will be subscribed by a group of TME Pharma shareholders and a corporate partner who have guaranteed the total gross proceeds of €2.6 million. The shareholders guaranteeing the operation share a goal to support the company and have declared that they do not act in concert, and to the best of the company’s knowledge do not have any related agreements between them. Net proceeds are expected to extend financial visibility of the company from January 2025 into June 2025. This financing aims to enable the completion of out-licensing, spin-out or a strategic transaction for both of the company’s compounds or to raise sufficient funds for continued development of NOX-A12 during this timeframe. The company expects to launch the upcoming public offer on December 12, 2024.

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"This planned guaranteed capital injection secures the operations of TME Pharma into June 2025 under its current plans, with the goal of completing ongoing initiatives with regards to licensing, financing, spin-out or a strategic transaction on both NOX-A12 and NOX-E36. Importantly, this equity raise will be structured to prioritize existing shareholders who have been supportive of the company. By participating, shareholders will have the opportunity to maintain their proportional investment in the company and thereby avoid dilution of their stakes, with any unsubscribed shares being guaranteed principally by other TME Pharma shareholders. This approach creates an attractive opportunity for supportive shareholders and also underlines the confidence of a significant shareholder group in the company," said Aram Mangasarian, CEO of TME Pharma. "The additional resources will allow us to leverage the latest statistically significant improvement in survival shown for the lead asset NOX-A12 in newly diagnosed brain cancer patients, which adds to the attractive profile of this agent including Fast-Track status in the US and orphan drug status in the US and EU. Furthermore, if a strategic transaction is determined to be the best course of action for one of the assets, we plan to return significant portion of funds obtained to shareholders as a dividend, once ongoing needs are covered. Should additional time be required beyond June 2025 to execute these transactions, the guarantors have indicated their intention to support the company under a significantly reduced operational cost structure. This contingency plan would involve transitioning to a virtual configuration with no permanent staff, outsourcing essential functions including maintaining readiness of the compounds for further development and pursuing business objectives. While this flexible approach demonstrates the long-term commitment of key investors to the company’s success, the primary goal remains to finalize a licensing deal, larger financing round with pharma or financial partner, spin-out, or strategic transaction before June 2025."

Certain details of the upcoming public offer:

Expected launch of the upcoming public offer: December 12, 2024.
Expected subscription period of the priority period: From December 12 to December 18, 2024 (inclusive).
The capital increase will be carried out without shareholders’ preferential subscription rights however with the right for current shareholders as at the record date of December 10, 2024, to subscribe on a reducible basis. The last date to become the company’s shareholder on the record date in order to be able to participate in the public offer will be December 06, 2024 (T+2)1. These subscription rights are neither transferable nor negotiable.
Subscription right: for each four (4) shares held on the record date of December 10, 2024, close of business, shareholders are entitled to purchase five (5) newly issued shares at a price of €0.05 per share, representing a 67.82% discount vs. the closing price of €0.1554 of the company’s shares on December 03, 2024.
Shareholders who wish to participate in the public offer are advised to contact their financial intermediary as soon as possible following the official launch of the public offer as they may require action before the end of the priority period on December 18, 2024.
The guarantors in the aggregate will receive as compensation a fee equal to €182,000, which represents 7% of the total amount of €2.6 million that they guarantee, whether or not the full amount is called by TME Pharma.
The upcoming public offer will be exempted under the EU Prospectus Regulation (see: View Source) and the Dutch Exemption Regulations pursuant to the Financial Supervision Act (Vrijstellingsregeling Wft) (considering total consideration will be less than €5 million). The information document as prepared specifically for this transaction as required by and in accordance with the guidelines of the Dutch Authority for the Financial Markets and describing the key strategic, operational and financial risks will be published upon launch of the public offer on the investors page on TME Pharma’s website.
Certain risk factors associated with the public offer:

Shareholders who will not participate by subscribing would see their stake in the company’s share capital diluted.
The market price of the company’s shares may fluctuate and fall below the subscription price of the new share.
The volatility and liquidity of the company’s shares may fluctuate significantly.
The public offer is not subject to a performance guarantee and investors who have acquired subscription rights could sustain a loss equal to the price of acquiring these subscription rights.
If no shareholders other than the guarantors participate in the investment, the guarantors will fund the full guaranteed investment amount against the issuance of 52,000,000 shares, increasing their shareholding in the issuer amongst them from currently 11% to approximately 60% of the total issued and outstanding share capital of the issuer after the transaction. Each guarantor acts as an individual and the guaranteed investment amount does not represent a concerted action towards the potential control of the issuer. None of them individually would cross threshold of 50% ownership even if the guaranteed investment amount was required in full.
Certain risk factors associated with the company:

TME Pharma may not succeed in achieving a licensing, financing, spin-out or a strategic transaction on either compound by June 2025, or at all.
If TME Pharma transitions to a virtual configuration after June 2025 with minimal outsourced staffing, it may lose access to experienced staff, which may adversely affect its ability to execute business and operational functions.
TME Pharma expects to incur losses for the foreseeable future and it, or its partners, will need substantial additional funding in order to complete the development and commercialization of its product candidates, which may not be available on acceptable terms when needed, if at all.
If TME Pharma is not successful in obtaining funds via completion of licensing, financing, spin-out or a strategic transaction or by raising additional funds as of June 2025, there is substantial risk that TME Pharma will be unable to continue as a going concern and may face liquidation or dissolution.
Important legal information:
The release, publication or distribution of this announcement in certain jurisdictions may be restricted by law and therefore persons in such jurisdictions into which they are released, published or distributed, should inform themselves about, and observe, such restrictions.

This announcement contains information relating to an intended offering by TME Pharma N.V. that will be exempted under the Regulation (EU) 2017/1129 of the European Parliament and of the Council of June 14, 2017 and the Dutch Exemption Regulations pursuant to the Dutch Financial Supervision Act (Vrijstellingsregeling Wft) (considering total consideration will be less than €5 million).

This announcement does not constitute or form a part of any offer or solicitation to purchase or subscribe for securities in the United Kingdom, United States, Australia, Canada, or Japan or in any jurisdiction in which such offers or sales are unlawful. Any securities have not been and will not be registered under the U.S. Securities Act of 1933, as amended (the "Securities Act"), or under any applicable securities laws of any state, province, territory, county or jurisdiction of the United Kingdom, United States, Australia, Canada, or Japan.