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Anixa Biosciences Initiates Dosing in Third Cohort in its Ovarian Cancer CAR-T Clinical Trial

On November 18, 2024 Anixa Biosciences, Inc. ("Anixa" or the "Company") (NASDAQ: ANIX), a biotechnology company focused on the treatment and prevention of cancer, reported that it has dosed its first patient in the third cohort in the ongoing Phase 1 clinical trial of its novel chimeric antigen receptor-T cell (CAR-T) therapy for recurrent ovarian cancer (Press release, Anixa Biosciences, NOV 18, 2024, View Source [SID1234648465]). The study is being conducted through a research partnership with Moffitt Cancer Center ("Moffitt").

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No dose limiting toxicity was observed in the initial three-patient cohort or in the second three-patient cohort, in which patients received a CAR-T cell dose triple that of the first cohort. After the required one-month waiting period to assess the occurrence of dose limiting toxicity and review of all safety data, the trial has now dosed its first patient in the third cohort at a tenfold increase over the initial dose.

Anixa’s FSHR-mediated CAR-T technology targets the follicle-stimulating hormone receptor (FSHR), which research indicates is exclusively expressed on ovarian cells, tumor vasculature, and certain cancer cells. The first-in-human trial (NCT05316129) is enrolling adult women with recurrent ovarian cancer who have progressed on at least two prior therapies. The study is designed to evaluate safety and identify the maximum tolerated dose, while monitoring efficacy.

Dr. Robert Wenham, principal investigator of the study and Chair of the Department of Gynecologic Oncology at Moffitt, stated, "With no dose-limiting safety issues observed in the first and second patient cohorts, we have advanced to the next cohort to evaluate a 10x higher dose compared with the starting dose. As the trial continues, our aim is to demonstrate the tolerability of our CAR-T but we are optimistic and hopeful about seeing efficacy in this solid tumor—a challenging area for traditional CAR-T therapies, which have shown efficacy mainly in hematologic tumors and lymphomas. We are very encouraged how the trial has progressed and our observation in one patient from the first cohort who had relative stability and even some mild improvement for well over a year after her infusion. This is highly unusual for a platinum resistant multiply treated ovarian cancer. A tumor biopsy showed necrosis and T cell infiltration. Based on these findings, we recently submitted an amendment to the trial protocol to allow patients who may benefit from an additional dose. Generally, we expect higher cell doses to increase efficacy, although we also anticipate a second dose may further improve response rates and durability. We are proud of the progress to date and look forward to treating additional patients in the third cohort."

Alentis Receives FDA Fast Track Designation for ALE.P02 for the Treatment of CLDN1+ Squamous Solid Tumors

On November 18, 2024 Alentis Therapeutics ("Alentis"), the clinical-stage biotechnology company developing treatments for Claudin-1 positive (CLDN1+) tumors and organ fibrosis, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to ALE.P02 for the treatment of advanced or metastatic CLDN1+ squamous cancers irrespective of the organ of origin (Press release, Alentis Therapeutics, NOV 18, 2024, View Source [SID1234648462]). ALE.P02 is an investigational antibody-drug conjugate (ADC) targeting CLDN1, developed for CLDN1+ squamous cancers including but not limited to lung, head and neck, cervical and esophageal cancers.

"We are encouraged by the FDA’s recognition of ALE.P02’s potential as a treatment for CLDN1+ squamous cancers," said Roberto Iacone, Chief Executive Officer of Alentis Therapeutics. "It reflects the importance of advancing ALE.P02 through clinical development, and it brings us one step closer to providing a new treatment option for patients."

Fast Track designation is designed to expedite the development and review of drugs that treat serious or life-threatening conditions and demonstrate the potential to address unmet medical needs.

"We have set out to develop ALE.P02 in the most rational way, following CLDN1 science and the clinical understanding of squamous cancers. The FDA’s support in this endeavor is certainly motivating," added Luigi Manenti, Chief Medical Officer of Alentis. "We are optimistic about the potential of ALE.P02 and look forward to the start of our first-in-human clinical trial in Q1 2025."

"Squamous cancers of various origin have been shown to overexpress CLDN1, making ALE.P02 a promising ADC to address the unmet medical needs of these patients," said Tony Mok Professor of Clinical Oncology at the Chinese University of Hong Kong. "CLDN1 is an exciting new target for ADCs and Alentis has been the frontrunner in developing anti-CLDN1 therapeutics."

About ALE.P02
ALE.P02 is a first-in-class ADC designed by linking a tubulin inhibitor, a potent cancer drug, to our antibody that specifically targets a unique CLDN1 epitope exposed on cancer cells. This combination could be a powerful new tool to fight the many squamous cancers that overexpress CLDN1 with less toxicity than traditional cancer drugs. The IND application for ALE.P02 to commence a Phase 1/2 clinical trial in advanced or metastatic CLDN1+ squamous solid tumors was recently cleared by the FDA.

Entry into a Material Definitive Agreement

On November 17, 2024, HCW Biologics Inc. (the "Company") entered into an exclusive, worldwide License, Research, and Co-Development Agreement (the "License Agreement") with WY Biotech Co., Ltd. (the "Licensee") for one of the Company’s preclinical, proprietary molecules (the "Licensed Molecule"). Under the terms of the License Agreement, the Company will receive an upfront fee of $7.0 million, to be paid in two tranches (Filing, 8-K, HCW Biologics, NOV 17, 2024, View Source [SID1234648468]). Within 90 days after the effective date of the License Agreement, which may be extended by an additional 30 days, if required, the Licensee will pay the Company $4.0 million; and within 30 days of completing the technology transfer to the Licensee, the Company will receive $3.0 million. All payments under the License Agreement will be made in U.S. Dollars.

Upon the completion of a Phase 1 clinical trial in any jurisdiction, the Company has an "Opt-In Right," which gives the Company the option to assume all control and responsibility for the development, manufacture and commercialization of the Licensed Molecule in the Opt-In Territory. The "Opt-In Territory" is North America, South America, and Central America. Upon the completion of the exercise of the Opt-In Right, the Company will be responsible for all costs associated with research and development, manufacturing, clinical development, regulatory approval, and commercialization for the Licensed Molecule in the Opt-In Territory.

The Licensee will pay the Company milestone payments as the Licensed Molecule advances through clinical trials and the first marketing approval is granted for the first territory in which the Licensee retains exclusive rights. Upon commercialization, the Company will receive double-digit royalties on a product-by-product basis in each jurisdiction in which the Licensee retains exclusive rights, subject to adjustment in the event the Company exercises the Opt-In Right. In addition, the Company will share a substantial portion of the net proceeds from any future transactions entered into by the Licensee, involving an exclusive license for the Licensed Molecule, an assignment of the License Agreement or the sale of the Licensee’s business that would permit the buyer to assume exclusive rights under the License Agreement, excluding transactions in the Greater China market. The Company and the Licensee have expressed their intent to work cooperatively with respect to the Licensed Molecule in the development stage, with a global focus for clinical development and partnering. The License Agreement contains various representations, warranties, affirmative and negative covenants, events of default and related remedies as well as other customary provisions.

The foregoing summary of the terms of the License Agreement does not purport to be complete.

Ascentage Pharma Announces a New Drug Application for Its Novel Bcl-2 Inhibitor Lisaftoclax Accepted and Recommended Priority Review Designation by CDE of China NMPA

On November 17, 2024 Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in discovering, developing and commercializing therapies to address global unmet medical needs primarily for malignancies, reported that a New Drug Application (NDA) for its inhouse developed investigational novel Bcl-2 selective inhibitor, lisaftoclax (APG-2575), for the treatment of patients with relapsed or refractory (r/r) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) has been accepted and recommended the Priority Review designation by the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) (Press release, Ascentage Pharma, NOV 17, 2024, View Source [SID1234648450]). This NDA, the first for a domestically developed Bcl-2 inhibitor in China, could potentially lead lisaftoclax to become the second Bcl-2 inhibitor approved anywhere in the world.

This NDA is based on results from a pivotal registrational Phase II study in China (APG2575CC201) that evaluated the efficacy and safety of lisaftoclax in patients with r/r CLL/SLL. The primary endpoint of the study is the overall response rate (ORR).

CLL/SLL is a hematologic malignancy caused by mature B-cell neoplasms. It primarily affects older populations and is among the most common leukemia subtypes in the Western World, with over 100,000 new diagnoses reported globally each year1. In China, where the incidence rate of CLL/SLL is lower than that of the western countries, the disease is occurring at a rapidly rising rate, with a younger age of onset and higher aggressiveness2. SLL and CLL are two different manifestations of the same disease and approximately 20% of all SLL cases would progress to CLL3. Treatments such as immunotherapies and Bruton’s tyrosine kinase inhibitors (BTKis) have significantly improved patients’ responses to initial treatment. However, due to the limitations of existing treatment options, the poor prognosis of patients, severe impact on patients’ quality of life and high complexity of the disease, patients with r/r CLL/SLL are in desperate need for new treatment options that are safe and effective.

The introduction of Bcl-2 inhibitors has further revolutionized the treatment of CLL/SLL. Bcl-2 is an apoptosis suppressor factor that regulates cell survival by controlling mitochondrial membrane permeability. It suppresses apoptosis by inhibiting the release of cytochrome C from mitochondria or by binding to apoptotic activators to inhibit the activity of caspase. The overexpression of Bcl-2, found in a variety of hematologic malignancies, particularly CLL/SLL, is a key mechanism by which tumor cells evade apoptosis.

However, the development of Bcl-2 as a therapeutic target is challenging mainly because its mechanism of action is based on the protein-protein interaction (PPI). The binding interface of Bcl-2 is relatively large, making it difficult for small-molecule inhibitors to exert blocking effects. Additionally, the Bcl-2 protein is located on the mitochondrial membrane, and mitochondria, with its double-membrane structure, is among the most complex and challenging cellular components. Drugs must first penetrate the cell membrane before they can further act on the mitochondrial membrane. In nearly 40 years since the discovery of this target, only one Bcl-2 inhibitor has been approved globally, a reality highlighting the immense difficulty and challenges in this field of research and development. In western countries, the treatment of CLL/SLL has entered a new era of chemotherapy-free and fixed-duration regimens, while no Bcl-2 inhibitor has been approved in China in this therapeutic area. Therefore, patients in China have an urgent unmet need for such novel therapies that can offer both efficacy and safety.

Lisaftoclax is a novel, investigational orally administered small-molecule Bcl-2 selective inhibitor being developed by Ascentage Pharma to treat patients with malignancies by selectively blocking the antiapoptotic protein Bcl-2 and hence restoring the normal apoptosis process in cancer cells. Lisaftoclax is the first Bcl-2 inhibitor in China and the second anywhere globally that has demonstrated compelling clinical benefit and entered a pivotal registrational study. Lisaftoclax has broad therapeutic potential for a variety of hematologic malignancies and solid tumors, particularly as a single agent and in combinations in CLL/SLL. Lisaftoclax is a potential drug that may offer patients a safe, effective, and easy to use treatment option.

Lisaftoclax is being evaluated in multiple registrational Phase III studies, including a global registrational Phase III study of lisaftoclax in combination with a BTKi in previously treated patients with CLL/SLL (cleared by the US FDA); a global registrational Phase III study of lisaftoclax in combination with acalabrutinib for the first-line treatment of treatment-naïve patients with CLL/SLL; a global registrational Phase III study of lisaftoclax in combination with azacitidine (AZA) for the first-line treatment of elderly/unfit treatment-naïve patients with acute myeloid leukemia (AML) who were intolerant of standard induction chemotherapies; and a global registrational Phase III study of lisaftoclax in combination with AZA for the first-line treatment of newly-diagnosed patients with higher-risk myelodysplastic syndrome (MDS).

"Ascentage Pharma’s founding team has over 20 years of deep experience in developing apoptosis-targeted therapies and has made significant strides with the Bcl-2 target," said Dr. Dajun Yang, Chairman & CEO of Ascentage Pharma. "To date, only one Bcl-2 inhibitor has been approved globally, which is a reality underscoring the immense difficulty and challenges in this field of research and development. This NDA submission for lisaftoclax could potentially pave the way for lisaftoclax to become the first approved China-developed Bcl-2 inhibitor, thus marking another major milestone that is a culmination of the Ascentage Pharma’s deep commitment and perseverant work in the past 15 years."

Dr. Yang continued, "Globally, r/r CLL/SLL represents an area of urgent unmet clinical needs. To have successfully advanced lisaftoclax to this point, it is a true testament to Ascentage Pharma’s robust capabilities in global pharmaceutical innovation. Moving forward, we will accelerate the global development of lisaftoclax in other indications to bring benefit to patients as quickly as possible. Remaining steadfastly committed to our mission of addressing unmet clinical needs in China and around the world, we will strive to develop more novel therapeutics for patients in need."

St Vincent’s Hospital to conduct head-to-head trial with Clarity’s SAR-bisPSMA diagnostic product

On November 17, 2024 Clarity Pharmaceuticals (ASX: CU6) ("Clarity" or "Company"), a clinical-stage radiopharmaceutical company with a mission to develop next-generation products that improve treatment outcomes for children and adults with cancer, a clinical-stage radiopharmaceutical company with a mission to develop next-generation products that improve treatment outcomes for children and adults with cancer, reported a new Investigator-Initiated Trial (IIT), evaluating the performance of Clarity’s diagnostic product, 64Cu-SAR-bis-PSMA, in comparison to standard-of-care (SOC) 68Ga-PSMA-11 product for the detection of prostate cancer recurrence (Press release, Clarity Pharmaceuticals, NOV 17, 2024, View Source [SID1234648447]).

The trial, named Co-PSMA, stands for "Comparative performance of 64Copper [64Cu]-SAR-bis-PSMA vs 68Ga-PSMA-11 PET CT for the detection of prostate cancer recurrence in the setting of biochemical failure following radical prostatectomy". It is led by Prof Louise Emmett at St Vincent’s Hospital, Sydney.

The Co-PSMA trial is a prospective, Phase II comparative imaging trial in 50 patients with biochemical recurrence (BCR) post-radical prostatectomy who are being considered for curative salvage radiotherapy. The primary objective of the study is to compare the detection rate of sites of prostate cancer recurrence, as determined by number of lesions per patient, between 64Cu-SAR-bisPSMA and 68Ga-PSMA-11 positron emission tomography (PET)/computed tomography (CT).

Prof Louise Emmett has been a member of Clarity’s Scientific Advisory Board since 2022 and is deeply embedded in Australia’s multidisciplinary clinical development and cancer research efforts. She is passionate about translational science, collaborating with biotechnology companies to bring promising theranostic agents into the clinic. Prof Emmett was Lead Principal Investigator in Clarity’s successfully completed Phase I diagnostic 64Cu-SAR-bisPSMA trial in patients with untreated prostate cancer, PROPELLER1, which led to the registrational Phase III CLARIFY trial (NCT06056830)2, currently recruiting patients in the U.S. and Australia. She also led 2 IITs with Clarity’s SAR-Bombesin product in prostate and breast cancer indications, BOP3 and C-BOBCAT4 trials, respectively.

Dr Alan Taylor, Executive Chairperson of Clarity Pharmaceuticals, commented: "We are excited to deepen our collaboration with Prof Louise Emmett and St Vincent’s Hospital, Sydney, through this new investigator-initiated Phase II trial. We pride ourselves on good Australian science and adhering to the highest standard for clinical research, so we look forward to working with Prof Emmett on generating data to highlight the benefits of our bisPSMA molecule over the current-generation diagnostics, such as the generic 68Ga-PSMA-11. Through this IIT we also look to provide access to what we consider to be the best-in-class diagnostic to more men suffering from prostate cancer in Australia, and particularly in our home city of Sydney.

"The head-to-head comparison between 64Cu-SAR-bisPSMA and 68Ga-PSMA-11 PET presents a significant opportunity to continue demonstrating the superior diagnostic capabilities of our proprietary copper-based and bis-PSMA platforms. 64Cu-SAR-bisPSMA’s excellent performance has already been demonstrated in the COBRA trial5, where we were able to image lesions more than 6 months prior to other standard of care imaging, identifying lesions with a diameter smaller than 2 millimetres. We know very well that early detection of cancer provides the best opportunities for better treatments, and this capability, coupled with the extended imaging window and logistical advantages, make it an ideal candidate to revolutionise care in these patients."

Prof Louise Emmett (St Vincent’s Hospital Sydney), Principal Investigator in the Co-PSMA trial, commented: "Men with BCR after radical prostatectomy have a window of opportunity for a cure with the use of external beam radiotherapy. In order to achieve that, we need to use highly sensitive imaging techniques that can accurately detect the site of disease recurrence when the prostate-specific antigen (PSA) levels start to rise. This could really help improve patients’ lives, and I am really looking forward to seeing whether the use of 64Cu-SAR-bisPSMA has a significant management impact over the current standard 68Ga-PSMA-11 PET CT, detecting sites of disease recurrence more accurately."