AskGene Announces Completion of First Human Dosing of ASKG315, The First IL-15 Prodrug in Clinical Development

On December 30, 2022 AskGene Pharma Inc. reported that the first patient completed their first dose (Cycle 1, Day 1) in the phase I clinical trial of ASKG315 in Shanghai, China (Press release, AskGene Pharmaceuticals, DEC 30, 2022, View Source [SID1234625682]). The study is an open label, multicenter phase I clinical trial evaluating the safety, tolerability, and pharmacokinetics of ASKG315 for injection in patients with locally advanced or metastatic solid tumors. ASKG315 is the first IL-15 prodrug in clinical development in the world.

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Jian-Feng (Jeff) Lu, Ph.D., CEO of AskGene commented: "ASKG315 is the second cytokine prodrug incubated from our propriety SmartKine cytokine prodrug platform technology. Preclinical data showed that ASKG315 selectively stimulated NK cells and CD8+ T cells. We are looking forward to achieving initial clinical proof of concept of the molecule as well as the platform. With multiple clinical programs, AskGene is establishing its global leading position in the field of cytokine prodrug."

Barbara Hickingbottom, J.D., M.D., Chief Medical Officer of AskGene commented: "Cytokines are natural immune stimulants, which cannot be used widely due to their short half-lives and narrow therapeutic windows. AskGene expects to use its proprietary technology to overcome these challenges. With the recent clearance of the ASKG915 IND by FDA, and an IL-2 prodrug in clinical development through a partnership, AskGene now has three cytokine prodrug programs in clinical development. We are very excited about the progress made in 2022 and look forward to the upcoming POC data from our clinical studies in 2023".

About ASKG315

ASKG315 is a novel and proprietary IL-15 prodrug discovered and developed by AskGene. It is the world’s first IL-15 prodrug moved into clinical development. Preclinical data of ASKG315 showed that this molecule selectively stimulated NK cells and CD8+ T cells in cynomolgus monkeys. Compared to previous generations of cytokine drugs, the prodrug design significantly extended the half-life, effectively improved the safety window, and reduced toxicity. ASKG315 has the longest half-life in cynomolgus monkeys among similar cytokine drugs in development.

AskGene Announces Clearance of IND Application by US FDA for ASKG915, A First-in-Class Anti-PD-1-IL-15 Prodrug Fusion Molecule for the Treatment of Patients with Solid Tumors

On December 30th, 2022 AskGene Pharma Inc. reported that the United States Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application for the clinical development of ASKG915, a novel and proprietary anti-PD-1-IL-15 prodrug fusion molecule for the treatment of cancer (Press release, AskGene Pharmaceuticals, DEC 30, 2022, View Source [SID1234625681]). Under this IND, AskGene will soon initiate a phase 1 study in the United States to investigate the safety, tolerability, pharmacokinetics, and efficacy of ASKG915 in patients with advanced solid tumors. ASKG915 will be the first anti-PD-1-IL-15 prodrug fusion molecule moving into clinical development in the world.

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Jian-Feng (Jeff) Lu, Ph.D., CEO of AskGene commented: "We are pleased that we received IND clearance for ASKG915, which is our third cytokine prodrug program entering clinical development. This important milestone brings us closer to delivering a truly bifunctional molecule with synergistic effect of an IL-15 agonist and PD-1 blockage to treat oncology patients. ASKG915 is expected to benefit patients who do not respond to current immunotherapies."

About ASKG915

ASKG915 is the world’s first PD-1 antibody-IL-15 prodrug fusion molecule to enter clinical development. The molecule can achieve tumor targeting through the anti-PD-1 antibody and be locally activated at the tumor site. It is also designed to allow high enough of a dosage so that the anti-PD-1 antibody has full PD-1 blockage functionality. Preclinical data showed that ASKG915 has extended PK, significantly better efficacy than an anti-PD-1 antibody monotherapy, and an expanded therapeutic window. ASKG915 is expected to benefit patients who are not responding to existing anti-PD-1 antibody therapies. A Phase I clinical trial is expected to start in the first half of 2023.

Chinese Clinical Trials of PSMA-targeted RLT Drug for Metastatic Prostate Cancer Are Approved

On December 28, 2022, Sinotau Pharmaceutical reported the clinical trial application for [177Lu]Lu-XT033 injection, a class I new drug developed by Sinotau, was approved, which means [177Lu]Lu-XT033 is one step closer to commercialization and clinical application (Press release, Sinotau Pharmaceutical, DEC 29, 2022, View Source [SID1234639241]).

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The project has already initiated ethical filing and other preparations, and will advance to clinical enrollment as soon as possible.

[177Lu]Lu-XT033 injection, which is another milestone in the innovative development of radionuclide therapeutic drugs in China, will benefit patients with metastatic prostate cancer and is a new option and hope in the field of precision therapy for metastatic prostate cancer.

About [177Lu]Lu-XT033 injection

[177Lu]Lu-XT033 injection is a radioligand therapy (RLT) drug intended for the treatment of adult patients with metastatic prostate cancer whose prostate specific membrane antigen (PSMA) is positive. RLT was introduced in the 1940s and works by combining a targeting compound (ligand) with a therapeutic radioisotope (radioactive particle). When injected into the bloodstream, the radioligand binds to the tumor so that the radiation produced is more locally focused on the tumor tissue, reducing damage to other healthy tissues of peripheral and whole body. The radioisotope, which acts as therapeutic agent, can disrupt tumor cell replication or trigger tumor cell death. Compared with traditional radiotherapy for tumors, RLT therapy has the advantages of precise targeting, powerful killing and limited damage, and plays a crucial role in the treatment of tumors in clinical practice.

PSMA is an ideal target for prostate cancer precision therapy. The world’s first PSMA-targeted prostate cancer RLT drug, 177Lu-PSMA-617 (trade: Pluvicto) developed by Novartis, was approved for marketing in the U.S. on March 23, 2022. In 2018, Novartis acquired Endocyte for $2.1 billion and acquired this product. Results from a subsequent global phase III clinical trial showed that 177Lu-PSMA-617 significantly improved overall survival (OS) and radiologic progression-free survival (rPFS) in patients with PSMA-positive mCRPC and reduced the risk of death for patients by 38% compared to the best standard of care.

177Lu-labeled PSMA-targeted RLT drugs can specifically bind prostate-specific membrane antigen (PSMA) to achieve enrichment of the active ingredient at the prostate tumor site and kill tumor cells using beta-rays emitted by [177Lu] lutetium decay, causing DNA damage, disrupting the replication ability of tumor cells and/or triggering cell death, thus achieving precise treatment of metastatic prostate cancer adult patients. [177Lu]Lu-XT033 injection innovates on the basis of 177Lu-PSMA-617 by introducing an albumin affinity group-Evans blue (EB), with a view to achieving increased drug uptake in the target tumor and enhancing its anti-tumor activity.

Prostate cancer is the second most common cancer in men, and the fifth most common cause of cancer death in men. In recent years, the incidence of prostate cancer in China has been on a significant rise, with an incidence rate of 9.92/100,000, which means that there are nearly 9.8 prostate cancer patients among 100,000 people. Although the incidence of prostate cancer in China is lower than that in Western countries, the proportion of patients with advanced stages at diagnosis is higher than that in Western countries.

Notice of Delisting or Failure to Satisfy a Continued Listing Rule or Standard; Transfer of Listing.

On December 22, 2022, Athersys, Inc. (the "Company") received a written notice (the "Notice") from the Listing Qualifications Department of The Nasdaq Stock Market LLC ("Nasdaq") that the Company is not in compliance with the requirement to maintain a minimum closing bid price of $1.00 per share, as set forth in Nasdaq Listing Rule 5550(a)(2) (the "Bid Price Requirement"), because the closing bid price of the Company’s common stock (the "Common Stock") was below $1.00 per share for 30 consecutive business days. The Notice does not impact the listing of the Common Stock on the Nasdaq Capital Market at this time (Filing, 8-K, Athersys, DEC 29, 2022, View Source [SID1234625672]).

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The Notice provided that, in accordance with Nasdaq Listing Rule 5810(c)(3)(A), the Company has a period of 180 calendar days from the date of the Notice, or until June 20, 2023, to regain compliance with the Bid Price Requirement. During this period, the Common Stock will continue to trade on the Nasdaq Capital Market. If at any time before June 20, 2023 the bid price of the Common Stock closes at or above $1.00 per share for a minimum of ten consecutive trading days, Nasdaq will provide written notification that the Company has achieved compliance with the Bid Price Requirement and the matter will be closed.

The Company is considering all available options to regain compliance with the Bid Price Requirement. However, there can be no assurance that the Company will be able to regain compliance with the rule or will otherwise be in compliance with other Nasdaq listing criteria. In the event the Company does not regain compliance by June 20, 2023, the Company may be eligible for an additional 180 calendar day compliance period to demonstrate compliance with the Bid Price Requirement. To qualify for the additional 180-day period, the Company will be required to meet the continued listing requirements for market value of publicly held shares and all other initial listing standards (with the exception of the Bid Price Requirement). In addition, the Company will need to provide written notice to Nasdaq of its intention to cure the deficiency during the second compliance period by effecting a reverse stock split, if necessary. If the Company does not qualify for the second compliance period or fails to regain compliance during the second 180-day period, then Nasdaq will notify the Company that its Common Stock is subject to delisting. At that time, the Company may appeal the delisting determination to a Nasdaq Hearings Panel.

Sesen Bio and Carisma Therapeutics Announce Substantial Increase to Expected Special Cash Dividend in Connection with Pending Merger

On December 29, 2022 Sesen Bio, Inc. (Nasdaq: SESN) and Carisma Therapeutics Inc. (Carisma), a privately-held, clinical stage biopharmaceutical company focused on discovering and developing innovative immunotherapies, reported an amendment to their previously announced merger agreement dated September 20, 2022 (Press release, Sesen Bio, DEC 29, 2022, View Source [SID1234625669]).

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Under the terms of the amended merger agreement, which has been unanimously approved by the Boards of Directors of both companies, the one-time special cash dividend expected to be paid to Sesen Bio stockholders will be increased to approximately $70 million, or approximately $0.34 per share, representing the amount of excess cash available after Sesen Bio meets a required net cash minimum of $75 million and represents an increase from the previously stated up to $25 million special cash dividend, or up to $0.12 per share. Carisma’s previously announced approximately $30 million financing remains committed and is expected to close concurrently with the merger.

As part of the amended merger agreement, the contingent value right ("CVR") payable to Sesen Bio stockholders has been amended to also include proceeds from any sale of Vicineum and Sesen Bio’s other preclinical assets, in addition to any proceeds from the milestone payment under the Roche Asset Purchase Agreement.

The issuance of the special cash dividend and CVR remain contingent on the closing of the pending transaction. Following completion of the incremental financing from Carisma’s key investors and subsequent completion of the merger, Sesen Bio stockholders are expected to own 25.2% of the pro forma company consistent with the exchange ratio formula set forth in the original merger agreement.

Dr. Thomas Cannell, President and Chief Executive Officer of Sesen Bio, said, "Since first announcing the merger, both companies have engaged extensively with Sesen Bio stockholders and continued to explore ways to deliver greater value in connection with the closing. The $45 million increase to the expected special cash dividend delivers even more direct and immediate cash value. Furthermore, Sesen Bio stockholders will be positioned to realize the long-term benefits of the pending merger, including a meaningful ownership position in the combined company, and benefit from additional potential upside through the CVR. With support from its financial and legal advisors, the Board embarked on a thorough evaluation of its strategic alternatives, including liquidation, and conducted outreach to more than 100 companies, 42 of which submitted bids. Based on this comprehensive review process, we are confident that the pending merger maximizes stockholder value and is in the best interest of our stockholders. In the weeks ahead, we look forward to further engaging with our stockholders regarding the significant benefits of our pending merger with Carisma."

Steven Kelly, President and Chief Executive Officer of Carisma, added, "The revised terms of our pending merger with Sesen Bio reinforce our confidence in and commitment to completing this compelling transaction. Carisma’s stockholders continue to be enthusiastic about the potential merger and have reaffirmed their commitment to provide incremental financing to support the combined company. Following completion of our merger with Sesen Bio, the combined company will be positioned for continued success as we advance our mission to revolutionize cancer treatments."

The merger and related financing are expected to close in the first quarter of 2023, subject to approval by Sesen Bio stockholders and other customary closing conditions.

Update on Engagement with Investor Group

On November 18, 2022, Bradley Radoff and Michael Torok and their affiliates (collectively, the "Investor Group") disclosed beneficial ownership of 5.7% of Sesen Bio’s outstanding common stock, indicated to Sesen Bio that it would not support the pending merger with Carisma on the terms set forth in the merger agreement and subsequently demanded the payment of a special cash dividend to Sesen Bio stockholders in the amount of $0.50 per share or approximately $100 million. On December 1, 2022, the Investor Group disclosed ownership of 7.4% of Sesen Bio’s outstanding common stock. Both Sesen Bio, Carisma, and the companies’ respective advisors have engaged with the Investor Group in an attempt to foster a constructive dialogue and reach an amicable resolution regarding the pending merger.

During such discussions, Sesen Bio and Carisma offered to significantly increase the amount of the special cash dividend by $45 million to approximately $70 million. This would increase the immediate value paid to Sesen Bio stockholders while providing the go-forward combined company with the necessary net cash of $75 million to fund its operations, based on an expected Sesen Bio net cash as of immediately prior to close and before issuance of the cash dividend of approximately $145 million.

The Sesen Bio Board of Directors continues to believe the merger provides Sesen Bio stockholders with both immediate value and future upside, which is far superior to the risk, uncertainty and prolonged timeline associated with Sesen Bio re-initiating a process to evaluate (or re-evaluate) potential strategic alternatives, including a liquidation. Based on the comprehensive review process conducted with the Sesen Bio Board of Directors, the payment of a special cash dividend without a concurrent transaction would be unlikely.

However, despite the offer to increase the expected special cash dividend to approximately $70 million from up to $25 million and the immediate value represented by the dividend, CVR and continued ownership in the combined company – and despite the parties and their advisors providing the above information – the Investor Group nonetheless continues to demand an approximate $100 million special cash dividend.

SVB Securities is acting as exclusive financial advisor to Sesen Bio for the transaction and Hogan Lovells US LLP is serving as its legal counsel. Evercore is serving as lead financial advisor to Carisma for the transaction and BofA Securities, Inc. is also serving as financial advisor to Carisma for the transaction. Wilmer Cutler Pickering Hale and Dorr LLP is serving as legal counsel to Carisma. BofA Securities, Inc. and Evercore are serving as co-placement agents for Carisma’s concurrent financing and Shearman & Sterling LLP is serving as the placement agents’ legal counsel.