On November 18, 2024 European Medicines Agency (EMA)’s Committee for Medicinal Products for Human Use (CHMP) reported to have adopted a positive opinion recommending the approval of Sarclisa in combination with bortezomib, lenalidomide, and dexamethasone (VRd) for the treatment of adult patients with newly diagnosed multiple myeloma (NDMM) who are ineligible for autologous stem cell transplant (ASCT) (Press release, Sanofi, NOV 18, 2024, View Source [SID1234648476]). A final decision is expected in the coming months.

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Dietmar Berger, M.D., Ph.D.

Chief Medical Officer, Global Head of Development at Sanofi

"The positive CHMP opinion is an important step forward for people with transplant-ineligible newly diagnosed multiple myeloma for whom effective front-line therapy may improve long-term outcomes. If approved, this Sarclisa-based combination could establish a new standard-of-care treatment approach for patients in the EU, helping to address a critical care gap in multiple myeloma treatment, and reinforcing Sarclisa’s potential as the anti-CD38 therapy of choice."

In September 2024, the US Food and Drug Administration (FDA) approved Sarclisa in combination with VRd for the treatment of adult patients with NDMM who are not eligible for ASCT, representing the first global approval for Sarclisa in the first line setting. In addition, the FDA granted orphan drug exclusivity for Sarclisa in the approved indication.

Sarclisa is currently approved in two indications for the treatment of certain adult patients with relapsed or refractory MM in more than 50 countries, including the US and EU.

First positive global phase 3 study combining anti-CD38 therapy with VRd to significantly improve PFS versus VRd alone in transplant-ineligible NDMM supports CHMP decision

The positive CHMP opinion is based on data from the IMROZ phase 3 study, which was presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2024 annual meeting, European Hematology Association (EHA) (Free EHA Whitepaper) 2024 meeting, and published in The New England Journal of Medicine. IMROZ is the first global phase 3 study of a CD38 monoclonal antibody in combination with standard-of-care VRd to significantly improve progression-free survival (PFS) versus VRd alone. The safety and tolerability of Sarclisa observed was consistent with the established safety profile of Sarclisa and VRd with no new safety signals.

About Sarclisa

Sarclisa (isatuximab) is a CD38 monoclonal antibody that binds to a specific epitope on the CD38 receptor on MM cells, inducing distinct antitumor activity. It is designed to work through multiple mechanisms of action including programmed tumor cell death (apoptosis) and immunomodulatory activity. CD38 is highly and uniformly expressed on the surface of MM cells, making it a target for antibody-based therapeutics such as Sarclisa. In the US, the non-proprietary name for Sarclisa is isatuximab-irfc, with irfc as the suffix designated in accordance with nonproprietary naming of biological products guidance for industry issued by the US FDA.

Currently Sarclisa is approved in more than 50 countries, including the US and EU, across two indications; Sarclisa is approved under an additional indication in the US. In Europe, based on the ICARIA-MM phase 3 study, Sarclisa is approved in combination with pomalidomide and dexamethasone for the treatment of patients with relapsed refractory MM (RRMM) who have received ≥2 prior therapies, including lenalidomide and a proteasome inhibitor and who progressed on last therapy. Based on the IKEMA phase 3 study, Sarclisa is also approved in 50 countries in combination with carfilzomib and dexamethasone, including in the US for the treatment of patients with RRMM who have received 1–3 prior lines of therapy and in the European Union for patients with MM who have received at least 1 prior therapy. In the US, Sarclisa is also approved in combination with VRd as a first line treatment option for adult patients with NDMM who are not eligible for ASCT, based on the IMROZ phase 3 study.

Sanofi continues to advance Sarclisa as part of a patient-centric clinical development program, which includes several phase 2 and phase 3 studies across the MM treatment continuum spanning six potential indications. In addition, the company is evaluating a subcutaneous administration method for Sarclisa in clinical studies. The safety and efficacy of Sarclisa has not been evaluated by any regulatory authority outside of its approved indications and methods of delivery.

In striving to become the number one immunoscience company globally, Sanofi remains committed to advancing oncology innovation. Through focused strategic decisions the company has reshaped and prioritized its pipeline, leveraging its expertise in immunoscience to drive progress. Efforts are centered on difficult-to-treat cancers such as select hematologic malignancies and solid tumors with critical unmet needs, including multiple myeloma, acute myeloid leukemia, certain types of lymphomas, as well as gastrointestinal and lung cancers.

On November 18, 2024 Cancer Targeted Technology (CTT), a privately-held Seattle-based biotechnology firm focusing on cancer diagnostics and therapeutics, reported that the National Cancer Institute awarded the Phase I portion ($400K) of the fast track Phase I/II ($2.4M) Small Business Innovation Research (SBIR) grant to develop a new drug to treat metastatic prostate cancer (Press release, Cancer Targeted Technology, NOV 18, 2024, View Source [SID1234648491]). The grant focuses on a promising new prodrug, CTT2274, that targets Prostate-Specific Membrane Antigen (PSMA) on prostate cancer and is designed to release a toxic drug, MMAE, within the cell that takes up the prodrug. PSMA is over-expressed on prostate cancer and expression increases as the cancer metastasizes and becomes castrate resistant. CTT’s unique phosphoramidate-based agents, bind irreversibly to PSMA and unlike other agents targeting PSMA, this distinctive mode of binding enhances uptake and internalization by tumor cells, leading to increased accumulation of the therapeutic payload and improved efficacy.

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Studies to date using CTT2274 treatment of mice bearing human prostate tumors have shown remission of tumor growth and an overall increase in survival. In addition, because of the prodrug release within the tumor cells, safety of the drug, at doses that are effective at inhibiting or reversing tumor growth, is excellent. In the Phase I portion of the grant, to be completed in Q2 2025, CTT will conduct additional non-clinical efficacy studies and manufacturing optimization. In Phase II of the grant, to be completed in Q2, 2026, CTT will conduct additional manufacturing and safety assessments necessary to advance CTT2274 to an Investigational New Drug (IND) application. These IND studies will support the initial clinical trial in metastatic prostate cancer planned for 2026.

"CTT2274 has a unique structure and linker that maximizes tumor uptake and allows for release of the chemotherapeutic drug only within the tumor cell thus minimizing potential side effects from the chemotherapy. No other prodrug like this is being developed for prostate cancer and CTT2274 holds great promise as a future treatment for men suffering from prostate cancer." stated Dr. Beatrice Langton-Webster, CEO of CTT and Principal Investigator on the grant. Visit CTT’s website at View Source to learn more about CTT2274.

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.

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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.

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]).

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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."

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.

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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."