TME Pharma Announces Corporate Strategy Update and Upcoming €2.6 Million Guaranteed Financing With Intention to Launch Public Offer Open Only to Shareholders to Enable Completion of Transactions Around NOX-A12 and NOX-E36 by June 2025

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.

Avistone Announces Updates on ANS03

On December 4, 2024 Beijing Avistone Biotechnology Co., Ltd (also referred to as "Avistone Biotechnology" or "Avistone"), an innovative biotechnology company focused on precision oncology therapeutics, reported that the United States Food and Drug Administration (FDA) has cleared the investigational new drug (IND) application for ANS03, a next generation tyrosine kinase inhibitor (TKI) targeting both ROS proto-oncogene 1 (ROS1) and neurotrophic tropomyosin receptor kinase (NTRK) (Press release, Avistone Pharmaceuticals, DEC 4, 2024, View Source [SID1234648818]).

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To date, a number of ROS1/NTRK inhibitors (such as crizotinib, entrectinib, larotrectinib and repotrectinib) have been approved by the US Food and Drug Administration (FDA) and China’s National Medical Products Administration (NMPA) for the treatment of patients with metastatic NSCLC whose tumors are ROS1/NTRK-positive. Despite the clinical activity of ROS1/NTRK TKIs, resistance invariably develops, and nonclinical/clinical studies have identified ROS1/NTRK kinase domain point mutations that result in the resistance of ROS1/NTRK fusion-positive cancers to ROS1/NTRK TKIs. Therefore, there is an urgent clinical need for novel Type II ROS1/NTRK TKIs capable of overcoming acquired resistance mutations, particularly solvent front (SF) mutations like ROS1-G2032R and ROS1-D2033N and NTRK1-G595R, as well as ROS1 central beta sheet #6 (Cβ6) mutation L2086F and NTRK1 xDFG mutation G667C.

As a type II inhibitor, ANS03 possesses a broader spectrum of resistance mutation inhibition, occupying not only the ATP-bound pocket of the kinase with the "DFG-out" inactive conformation but also extending into the adjacent allosteric pocket, thereby conferring ANS03 a distinctive pharmacodynamic advantage.

ANS03 was specifically designed to provide patients afflicted with ROS1/NTRK fusion mutant cancers with a best-in-class, oral, small molecule therapy that can effectively overcome the acquired drug resistance problems caused by type I TKIs and also possesses a broader inhibitory range of ROS1/NTRK kinase activity, including wild-type ROS1/NTRK fusion and numerous acquired drug-resistant mutations. Enrollment of patients with locally advanced or metastatic tumors harboring a ROS1 or NTRK alteration is expected to begin in Q1 2025.

Rondo Therapeutics Announces Collaboration with Lilly to Develop Novel CD28 Bispecific Antibodies for Solid Tumors

On December 4, 2024 Rondo Therapeutics, a privately held biopharmaceutical immuno-oncology company pioneering the development of next-generation T cell-engaging bispecific antibodies for the treatment of solid tumors, reported a research collaboration and license agreement with Eli Lilly and Company (Press release, Rondo Therapeutics, DEC 4, 2024, View Source [SID1234648817]). This collaboration will combine Rondo Therapeutics’ proprietary CD28 co-stimulatory platform with Lilly’s drug development and commercialization expertise to develop co-stimulatory bispecific antibodies for solid tumor treatment.

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"By combining Rondo’s innovative approach to immune T cell engagers with Lilly’s deep knowledge and resources in oncology, we believe this partnership has the potential to significantly impact the treatment landscape for solid tumors," said Shelley Force Aldred, CEO and co-founder of Rondo Therapeutics. "We are excited to collaborate with Lilly on our CD28 platform to advance the development of cancer therapies targeting solid tumors. Together, we are committed to accelerating the delivery of novel immuno-oncology therapies to the patients who need them most."

Under the terms of the agreement, Rondo Therapeutics will receive an undisclosed upfront cash payment and is eligible for additional development and commercial milestone payments, along with tiered royalties on commercial sales.

Rondo Therapeutics’ proprietary platform features CD28-targeting binders with a wide range of co-stimulatory potencies designed to boost T cell-mediated tumor killing and overcome T cell exhaustion in the solid tumor microenvironment. Rondo’s platform delivers bispecific antibody therapeutics tailored to specific tumor targets, indications, and treatment regimens, offering a transformative alternative to traditional "one size fits all" strategies, unlocking the potential for durable responses in patients with solid tumors.

Treovir and Matica Bio Forms Strategic Partnership to Advance Innovative Therapies for Pediatric Brain Tumors

On December 4, 2024 Matica Biotechnology (Matica Bio), a leading contract development and manufacturing organization (CDMO) specializing in viral vector development and manufacturing, reported a strategic partnerships with Treovir (Press release, Treovir, DEC 4, 2024, View Source [SID1234648816]). The collaboration aims to advance innovative therapies for pediatric patients with brain and other neurological cancers. Matica Bio will provide GMP manufacturing for clinical supplies.

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Treovir, a biotechnology company developing oncolytic immunotherapies, will partner with Matica Bio on its G207 HSV-based oncolytic therapy for treating glioblastoma and other brain tumors in children. The therapy is currently in Phase 2 clinical trials and could ultimately provide a treatment option for children in this critically underserved therapeutic area. "Finding a CDMO partner who truly understands our mission and works alongside us as an extension of our team is essential for successful drug development," said Michael Christini, CEO of Treovir. "We are collaborating with Matica Bio on process optimization and GMP clinical production for G207 and we look forward to advancing this promising therapy for pediatric brain tumors with Matica Bio playing a key role."

Matica Bio is committed to leveraging its expertise in gene therapy development and manufacturing to support the creation of treatment that address the unique challenges faced by children with rare diseases.

"We are thrilled to partner with Treovir in this important effort," said Paul Kim, CEO of Matica Bio. "Pediatric rare diseases represent an area of critical need, and Matica Bio is proud to contribute to the mission of improving the lives of these children. Our cutting-edge facilities and advanced manufacturing technologies provide the ideal foundation to help bring these life-changing therapies to market."

The collaboration reflects a shared commitment to addressing critical gaps in pediatric healthcare, ensuring that no child is left behind in the pursuit of better health outcomes.

Delta-Fly Pharma Inc.: Update for Development Status of DFP-17729

On December 4, 2024 Delta-Fly Pharma reported that as a result of consultation with the PMDA on December 3rd, 2024, the Phase II/III clinical trial of DFP-17729 in combination with TS-1 versus TS-1 alone in patients with pancreatic cancer after third-line treatment was approved (Press release, Delta-Fly Pharma, DEC 4, 2024, View Source [SID1234648815]).

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In a Phase I/II study of DFP-17729 in combination with TS-1 in patients with end-stage pancreatic cancer, no significant difference was observed against the control treatment (TS-1 or gemcitabine), but stratified analysis showed that when patients in the third-line or later treatment were treated for more than 6 weeks, DFP-17729 in combination with TS-1 showed a predominant median overall survival (mOS) prolongation (9.0 months vs. 6.1 months) and a significant correlation was also observed between urinary alkalinization and mOS in pancreatic cancer patients treated with DFP-17729, as key proof of concept. We had presented these results at the ESMO (Free ESMO Whitepaper) Gastrointestinal Cancers Congress 2024 and the 55 Annual Meeting of the Japan Pancreas Society, where much attention was paid to the presentation.

DFP-17729 is a novel approach to neutralize the acidic cancer microenvironment, and several patents on related inventions have been granted in major countries around the world, and its potential of efficacy has been published in peer-reviewed journals.

We will first identify DFP-17729 as a treatment for refractory pancreatic cancer, for which effective treatment is not yet available, and then seek to expand the indication to other types of cancer through partnership with major global pharmaceutical companies.