Clinical Trial Application (IND) for BioRay Pharmaceutical’s BR105 Injection Receives U.S. FDA Approval

On October 24, 2023 BioRay Pharmaceutical Co., Ltd. (hereinafter referred to as "BioRay") reported that its clinical trial application for BR105 Injection has received approval from the United States Food and Drug Administration (FDA) (Press release, BioRay Pharmaceutical, OCT 24, 2023, View Source [SID1234636312]). This marks BioRay’s first project to receive FDA IND approval.

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BR105 Injection is a humanized monoclonal antibody developed in-house, specifically targeting SIRPα. It can recognize common genotypes of SIRPα (V1, V2, V8) and disrupt the interaction between SIRPα and its ligand CD47, thereby abolishing the "don’t eat me" signal between macrophage and tumor cell. This activation enables macrophages to perform their tumor-phagocytosing function, achieving anti-tumor immunotherapy.

The efficacy of targeting CD47/SIRPα has been validated in various tumor models, and previous clinical studies suggest that targeting the CD47/SIRPα signaling pathway may have a broad spectrum of anti-tumor activity. CD47/SIRPα-targeted therapy has shown positive results in acute myeloid leukemia, lymphoma, head and neck squamous cell carcinoma, gastric cancer, and other malignancies.

Compared to CD47, the expression of SIRPα is more specific. By targeting SIRPα instead of CD47, BR105 exhibits enhanced safety profile intrinsically. Additionally, CD47 interacts with other proteins, such as TSP-1, SIRPγ, leading to a more complex signaling network and increased risks in corresponding targeted therapies. Therefore, developing SIRPα antibodies to block the CD47/SIRPα signaling pathway is a more promising strategy in oncology drug development. Currently, no medicine targeting SIRPα has been approved in the global market.

Phase I clinical trial of BR105 Injection is currently on-going in China, and preliminary result has confirmed its good clinical safety.

"Based on our global strategic layout of innovative drugs, the FDA IND approval of BR105 Injection as our first FDA approved clinical trial project is a significant milestone for BioRay. Currently, fierce competition exists in the global innovative drug discovery and development arena, where innovation is indispensable. BioRay continues to invest heavily in innovation and build a rich pipeline of innovative biopharmaceuticals," said by Dr. Wei Zhu, Chief Medical Officer of BioRay. "We look forward to transforming these pipelines and BR105 into best-in-class therapies in autoimmunology and immuno-oncology, benefiting an increasing number of patients both in China and overseas."

Caris Life Sciences and Moderna Announce Multi-Year Strategic Partnership to Advance mRNA-Based Oncology Therapeutics

On October 24, 2023 Caris Life Sciences(Caris), the leading next-generation AI TechBio company and precision medicine pioneer that is actively developing and delivering innovative solutions to revolutionize healthcare and improve the human condition using molecular science and AI, reported a new agreement with Moderna (NASDAQ:MRNA) in support of Moderna’s oncology and novel therapeutics initiatives (Press release, Caris Life Sciences, OCT 24, 2023, View Source [SID1234636311]).

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Through this multi-year agreement, Moderna will leverage Caris’ vast library of de-identified, multi-modal data solutions derived from whole exome sequencing, whole transcriptome sequencing and protein analyses along with claims data to enhance development strategies for Moderna’s oncology pipeline, including facilitation of optimal clinical trial design, discovery of novel biomarkers and characterization of resistance mechanisms.

"Partnering with Caris Life Sciences will support Moderna’s oncology portfolio with clinico-genomics data from Caris’ industry-leading and comprehensive suite of integrated precision medicine capabilities," stated Praveen Aanur, MD, MPH, MBA, Vice President, Oncology Therapeutic Area Head of Moderna.

"We are thrilled to partner with Moderna to impact and advance the field of cancer treatment with mRNA medicines, with a common goal of improving patient lives," said David Spetzler, MS, PhD, MBA, President of Caris Life Sciences. "The aggregate strength of our combined molecular, data science and therapeutics technologies will support the predictive modeling of patient responses to therapies, and more generally, may help improve the probability of technical and regulatory success of Moderna’s innovative medicines."

As the pioneer in precision medicine and molecular profiling, Caris has created the largest clinico-genomic database coupled with cognitive computing to unravel the molecular complexity of disease. Caris was the first in the industry to provide Whole Exome Sequencing DNA coverage and Whole Transcriptome Sequencing RNA coverage (WES / WTS) for every patient.

Citius Pharmaceuticals Executes Definitive Agreement to Merge Wholly Owned Subsidiary with TenX Keane Acquisition to Form Publicly Listed Citius Oncology, Inc.

On October 24, 2023 Citius Pharmaceuticals, a biopharmaceutical company developing and commercializing first-in-class critical care products, and TenX Keane Acquisition ("TenX") (NASDAQ: TENKU), a publicly traded special purpose acquisition company (SPAC), reported that they have entered into a definitive agreement, dated October 23, 2023, for a proposed merger of TenX and Citius Pharma’s wholly owned oncology subsidiary that will continue as a public company listed on the Nasdaq exchange (Press release, Citius Pharmaceuticals, OCT 24, 2023, View Source [SID1234636309]). The newly combined public company will be named Citius Oncology, Inc. ("Citius Oncology"). Upon closing, pursuant to the terms of the merger agreement, Citius Pharma would receive 67.5 million shares in Citius Oncology at $10 per share and retain majority ownership of approximately 90%. The transaction has been approved by the Board of Directors of both companies and is expected to close in the first half of 2024.

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Citius Oncology will serve as a platform to develop and commercialize novel targeted oncology therapies. The company is seeking approval from the U.S. Food and Drug Administration (FDA) of LYMPHIR for an orphan indication in the treatment of persistent or recurrent cutaneous T-cell lymphoma (CTCL), a rare form of non-Hodgkin lymphoma. Management estimates the initial market for LYMPHIR currently exceeds $400 million, is growing and is underserved by existing therapies. If approved, LYMPHIR would be unique as the only IL-2 receptor targeted CTCL therapy, offering a novel option to patients cycling through multiple treatments. Robust intellectual property protections that span orphan drug designation, complex technology, trade secrets and pending patents for immuno-oncology use as a combination therapy with checkpoint inhibitors would further support Citius Oncology’s competitive positioning.

Preparations are underway for a Biologics License Application (BLA) resubmission in early 2024. If approved, LYMPHIR could be commercially available as early as the second half of 2024 for the treatment of CTCL. Additional value creating opportunities in larger markets include potential indications in peripheral T-cell lymphoma or as a combination therapy with CAR-T and PD-1 inhibitors, and in markets outside the U.S. Currently, two investigator-initiated trials are underway to explore LYMPHIR’s potential as an immuno-oncology combination therapy.

The transaction is expected to provide Citius Oncology with improved access to the public equity markets and thereby facilitate the commercialization of LYMPHIR and position the company to explore additional value creating opportunities more fully.

CITIUS PHARMA AND TENX COMMENTS

"We believe this transaction will allow us to unlock the value of LYMPHIR, and solidly position Citius Pharma to advance our diversified pipeline. This transaction will enable Citius Oncology, with access to the broader capital markets, to better support the successful commercialization of LYMPHIR, if approved, and explore additional potential targeted oncology therapies. Our majority ownership position and shared services agreement ensures that the Citius Pharma management team will remain fully engaged with the development and commercialization efforts at Citius Oncology. As previously announced, the Company is in the process of formulating a plan of distribution of a portion of the shares of Citius Oncology to its shareholders. At Citius Pharma, we intend to focus on completing the Mino-Lok trial and continuing to evaluate next steps with our Halo-Lido program," stated Leonard Mazur, Chairman and CEO of Citius Pharma.

"We are very pleased to announce the proposed merger with Citius Oncology," said Mr. Xiaofeng Yuan, Chairman and CEO of TenX. "After undertaking a comprehensive process with external advisors to explore and evaluate numerous potential business combination targets, our board and management team believe that this transaction with Citius Oncology represents the best opportunity to create substantial value for our stockholders. This business combination, if consummated, will result in TenX investors owning an equity stake in a company that is focused on developing and commercializing LYMPHIR to improve the lives of patients with CTCL and additional potential upside from combinations with other drugs as immuno-oncology therapies with even larger addressable markets. We are thrilled to support Citius Oncology at an inflection point in its development and to provide an avenue for Citius to expeditiously meet its development milestones."

THE PROPOSED MERGER AGREEMENT

Pursuant to the proposed agreement, TenX will acquire Citius Pharma’s wholly owned subsidiary via a merger, with the newly combined publicly traded company to be named Citius Oncology, Inc. In the transaction, all shares of Citius Pharma’s wholly owned subsidiary would be converted into the right to receive common stock of Citius Oncology. As a result, upon closing, Citius Pharma would receive 67.5 million shares of common stock of Citius Oncology which, at an implied value of $10.00 per share, would be $675 million in equity of Citius Oncology, before fees and expenses. As part of the transaction, Citius Pharma will contribute $10 million in cash to Citius Oncology. An additional 12.75 million existing options will be assumed by Citius Oncology.

At closing, any cash remaining in TenX’s trust account along with the cash provided by Citius Pharma will be contributed to Citius Oncology to support ongoing operations and planned commercialization efforts. References to available cash from the TenX trust account and retained transaction proceeds are subject to any redemptions by the public stockholders of TenX and payment of transaction fees and expenses.

Upon closing, Citius Oncology will operate under a shared services agreement with Citius Pharma, with fees payable quarterly to Citius Pharma, for the services of several key members of the Citius Pharma team, led by Leonard Mazur, Chief Executive Officer, Jaime Bartushak, Chief Financial Officer and Dr. Myron Czuczman, Chief Medical Officer. Myron Holubiak will serve as Executive Vice Chairman of the Citius Oncology Board of Directors.

The transaction, which has been unanimously approved by both Boards of Directors of Citius Pharma and TenX, is subject to approval by stockholders of TenX and other customary closing conditions. Citius Pharma, as the sole holder of Citius Oncology common stock, has approved the transaction. The proposed business combination is expected to be completed in the first half of 2024.

A more detailed description of the transaction terms and a copy of the business combination agreement will be included in a Current Report on Form 8-K to be filed by each of Citius Pharma and TenX with the United States Securities and Exchange Commission ("SEC"). In connection with the transaction, TenX intends to file a registration statement (which will contain a proxy statement/prospectus) with the SEC.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy any of the securities described herein, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or jurisdiction.

CITIUS PHARMA AND TENX STOCKHOLDERS AND OTHER INTERESTED PERSONS ARE ADVISED TO READ, ONCE AVAILABLE, THE REGISTRATION STATEMENT AND THE PRELIMINARY PROXY STATEMENT/PROSPECTUS AND ANY AMENDMENTS THERETO AND, ONCE AVAILABLE, THE DEFINITIVE PROXY STATEMENT/PROSPECTUS IN CONNECTION WITH THE BUSINESS COMBINATION, BECAUSE THESE DOCUMENTS WILL CONTAIN IMPORTANT INFORMATION ABOUT CITIUS PHARMA, TENX, CITIUS ONCOLOGY AND THE PROPOSED MERGER.

ADVISORS

Maxim Group LLC is acting as exclusive financial advisor to Citius Pharma and Newbridge Securities Corporation is acting as exclusive financial advisor to TenX. Wyrick Robbins Yates & Ponton LLP is acting as legal advisor to Citius Pharma. The Crone Law Group P.C. is acting as legal advisor to TenX.

IMPORTANT INFORMATION ABOUT THE PROPOSED BUSINESS COMBINATION AND WHERE TO FIND IT

In connection with the proposed business combination, TenX intends to file a registration statement on Form S-4 that will include a proxy statement of TenX and a prospectus of Citius Oncology. The proxy statement/prospectus will be sent to all TenX stockholders. Before making any voting decision, securities holders of TenX are urged to read the proxy statement/prospectus and all other relevant documents filed or that will be filed with the SEC in connection with the proposed business combination as they become available because they will contain important information about the proposed business combination and the parties to the proposed business combination.

Investors and securities holders will be able to obtain free copies of the proxy statement/prospectus and all other relevant documents filed or that will be filed with the SEC by TenX and Citius Pharma through the website maintained by the SEC at www.sec.gov. In addition, the documents filed by Citius Pharma may be obtained free of charge from Citius Pharma’s website at www.citiuspharma.com, or by written request to Citius Pharmaceuticals, Inc., 11 Commerce Drive, 1st Floor, Cranford, New Jersey 07016, Attention Chief Financial Officer. The documents filed by TenX may be obtained free of charge by written request to TenX Keane Acquisition, 420 Lexington Avenue, Suite 2446, New York, New York 10170.

PARTICIPANTS IN THE SOLICITATION

Citius Pharma and Tenx and certain of their respective directors, executive officers, and other members of management and employees may, under SEC rules, be deemed to be participants in the solicitations of proxies from TenX’s shareholders in connection with the proposed transaction. Information regarding Citius Pharma’s directors and executive officers is available in its definitive proxy statement on Schedule 14A for the 2023 annual meeting of stockholders, which was filed with the SEC on December 22, 2022. Information about TenX’s directors and executive officers and their ownership of TenX’s securities is set forth in TenX’s filings with the SEC, including TenX’s Annual Report on Form 10-K for the fiscal year ended December 31, 2022, which was filed with the SEC on April 17, 2023. To the extent that holdings of TenX’s securities have changed since the amounts printed in TenX’s Annual Report, such changes have been or will be reflected on Statements of Change in Ownership on Form 4 filed with the SEC.

Additional information regarding the participants in the proxy solicitation and a description of their direct and indirect interests will be included in the proxy statement/prospectus when it becomes available. Shareholders, potential investors, and other interested persons in respect of Citius Pharma and TenX should read the proxy statement/prospectus carefully when it becomes available before making any voting or investment decisions. You may obtain free copies of these documents from the sources indicated above.

Avenge Bio to Present at the Society for Immunotherapy of Cancer (SITC) 38th Annual Meeting

On October 24, 2023 Avenge Bio, Inc. ("Avenge" or the "Company"), a biotechnology company developing the LOCOcyte Immunotherapy platform for the precision administration of potent immune effector molecules to treat solid tumors, reported their poster presentation at the Society of Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 38th Annual Meeting (SITC 2023) on November 1-5, 2023, in San Diego, California (Press release, Avenge Bio, OCT 24, 2023, View Source [SID1234636310]).

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In September 2023, Avenge Bio received FDA Fast Tack designation for AVB-001. AVB-001 is an encapsulated cell product engineered to produce native human interleukin-2 (hIL-2) and is delivered intraperitoneally (IP) to patients. Avenge is currently enrolling patients in a First-in-Human, Phase 1/2, multicenter clinical trial (NCT05538624) designed to evaluate the safety and efficacy of AVB-001. The Company has advanced through multiple dose levels in a dose escalation cohort and expects to initiate a Phase 2 dose expansion trial in 1H 2024.

Abstract #: 1045
Poster Title: Overcoming immunosuppressive tumors by stimulating the adaptive and innate immune systems
Presenting Author: Guillaume Carmona, PhD
Location: Exhibit Halls A and B1
Date: Friday, November 3, 2023
Time: 9:00 AM-7:00 PM PDT

The poster will present how a single administration of either AVB-001 or AVB-002, engineered to produce native human IL-2 or native human IL-12 respectively, demonstrated complete responses as monotherapy and provided sustained eradication in various mouse tumor models. In addition, the poster will also present the commonalities and differences between AVB-001 and AVB-002 in modulating the innate and adaptive anti-tumor immune response. The poster will be available on the Presentations and Publications section of www.avengebio.com following the conference.

About LOCOcyte Platform
Our LOCOcyteTM allogeneic cell-based immunotherapy platform enables potent localized modulation of the immune system which also precipitates a systemic immune response, allowing us to treat previously intractable cancers. The technology leverages three unique advantages:

(1) Potent immune effector molecules are generated by synthetically engineering allogeneic cells creating a ready-to-use therapy,

(2) Therapy is localized in proximity to the primary tumor site and generates innate and adaptive immune response, and

(3) The immunomodulator trains the patient’s immune system generating a robust immune response that seeks and eradicates distal metastasis without systemic toxicity.

Phase Ib/II Results of Akeso’s PD-1/CTLA-4 Bispecific Antibody for First-Line Treatment of Advanced Hepatocellular Carcinoma Published at 2023 ESMO

On October 24, 2023 Akeso reported poster presentation at the 2023 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress from its cadonilimab ( PD-1/CTLA-4 bispecific antibody) combined with lenvatinib for first-line treatment of Advanced Hepatocellular Carcinoma (HCC) (Press release, Akeso Biopharma, OCT 24, 2023, View Source [SID1234636308]). The principal investigators of the study are Prof. Bai Li and Prof. Jiao Shunchang of the Chinese PLA General Hospital.

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The results indicated that the novel combination therapy of PD-1/CTLA-4 bispecific antibody plus lenvatinib demonstrated promising efficacy and manageable toxicity that could provide an option of treatment in first-line treatment of advanced HCC. At the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, Akeso presented the preliminary therapeutic effect of cadonilimab combined with lenvatinib for first-line therapy of advanced HCC, showing promising anti-tumor activity and improved tolerability. The 2 years median follow-up results presented at the 2023 ESMO (Free ESMO Whitepaper) meeting further emphasized the efficacy of cadonilimab in improving overall survival (OS) among advanced patients.

Data Highlights:

Results demonstrated the outstanding efficacy of cadonilimab when combined with lenvatinib as a first-line treatment for HCC. The preliminary efficacy data outperformed those of approved therapies. As of July 28, 2023, the median follow-up period was 27.4 months.

When cadonilimab was dosed at 6 mg/kg Q2W, the objective response rate (ORR) was 35.5%, the median duration of response (mDoR) was 13.6 months, the median progression free survival (mPFS) was 8.61 months, and mOS was 27.1 months.
When the dose of cadonilimab was 15 mg/kg Q3W, the ORR was 35.7%, the mDoR was 13.7 months, the mPFS was 9.82 months, and the mOS was not yet reached.
The mPFS for first-line HCC treatment with the combination of cadonilimab and lenvatinib was higher compared to approved therapies. The study indicated that the improvement in PFS was more significant with the higher dose of cadonilimab (8.6 months at 6 mg/kg every 2 weeks vs. 9.8 months at 15 mg/kg every 3 weeks).
The adverse effects of the combination of cadonilimab and lenvatinib at all dosage levels were readily manageable without any new safety signals or cadonilimab-associated fatalities.
Akeso is currently conducting a randomized, double-blind, controlled Phase III clinical trial (AK104-306, NCT05489289) to evaluate the efficacy and safety of cadonilimab as adjuvant therapy for high-risk hepatocellular carcinoma after curative resection. The potential efficacy of cadonilimab for both operable and advanced HCC holds great promise for improving long-term survival rates for the entire HCC population.

About Cadonilimab(PD-1/CTLA-4 bispecific antibody)

Cadonilimab is a first-in-class bispecific antibody that targets both PD-1 and CTLA-4 developed by Akeso. It is a symmetric tetravalent bispecific antibody with a crystallizable fragment (Fc)-null design. In addition to demonstrating biological activity similar to that of the combination of CTLA-4 and PD-1 antibodies, cadonilimab possesses higher binding avidity in a high-density PD-1 and CTLA-4 setting than in a low-density PD-1 setting, while a mono-specific anti-PD-1 antibody does not demonstrate this differential activity. With no binding to Fc receptors, cadonilimab shows minimal antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, and interleukin-6 (IL-6)/IL-8 release. These features all likely contribute to significantly lower toxicities of cadonilimab observed in the clinic. Higher binding avidity of cadonilimab in a tumor-like setting and Fc-null design may lead to better drug retention in tumors and contribute to better safety while achieving anti-tumor efficacy.

Cadonilimab has been approved by the China National Medical Products Administration for recurrent or metastatic cervical cancer. Cadonilimab has been included and recommended in multiple clinical guidelines such as CSCO. In its first 12 months on the market, cadonilimab generated impressive sales revenue of 1.15 billion RMB. Cadonilimab has been engaged in more than 60 ongoing clinical trials including investigator-initiated studies. Patient enrollment has been completed for the phase 3 study of cadonilimab for first-line treatment of advanced cervical cancer as well as a phase 3 study of cadonilimab in combination with chemotherapy as first-line therapy in gastric cancer. A phase 3 study of cadonilimab as an adjuvant treatment for hepatocellular carcinoma is ongoing. Furthermore, a Phase 3 study comparing cadonilimab with chemotherapy to tislelizumab Injection with chemotherapy is underway for the first-line treatment of PD-L1 expression-negative non-small cell lung cancer.