Chronic lymphocytic leukemia- Pipeline Insight, 2024

Chronic lymphocytic leukemia- Pipeline Insight, 2024

DelveInsight’s, “Chronic lymphocytic leukemia- Pipeline Insight, 2024” report provides comprehensive insights about 55+ companies and 60+ pipeline drugs in Chronic lymphocytic leukemia pipeline landscape. It covers the pipeline drug profiles, including clinical and nonclinical stage products. It also covers the therapeutics assessment by product type, stage, route of administration, and molecule type. It further highlights the inactive pipeline products in this space.

Geography Covered

• Global coverage

Chronic lymphocytic leukemia: Understanding

Chronic lymphocytic leukemia: Overview

Chronic lymphocytic leukemia (CLL) is a malignancy of CD5+ B cells that is characterized by the accumulation of small, mature-appearing neoplastic lymphocytes in the blood, bone marrow, and secondary lymphoid tissues, resulting in lymphocytosis, leukemia cell infiltration of the bone marrow, lymphadenopathy, and splenomegaly. The exact etiology of CLL is unknown. Genetic factors, rather than environmental factors, are the most likely cause of CLL. However, few known risk factors for CLL include occupational causes by exposure to certain chemicals, radiation exposure, and tobacco users. Reports of farmers working around rubber manufacturing industries and workers with exposure to benzene and heavy solvents have shown an increased risk of CLL.

The pathogenesis of CLL is a two-step process that leads to the clonal replication of malignant B lymphocytes. The first step is the development of MBL cells secondary to multiple factors such as antigenic stimulation, genetic mutations, and cytogenetic abnormalities. The second step is the progression of MBL to CLL by the further insult to B-cell clone, either due to additional genetic abnormalities or changes in the bone marrow microenvironment. B-cell antigen receptor (BCR) expression induces antigen-independent, cell-autonomous signaling, which is an important step in the pathogenesis of CLL.

In CLL, CD5+ B cells are continuously activated by mutations leading to MBL. The accumulation of genetic abnormalities in more mature B cells causes a clonal division of the neoplastic B-cell within the lymph nodes. In CLL/SLL, the most common abnormal physical examination findings are lymphadenopathy, which is seen in 50 to 90% of patients. Cervical, supraclavicular, and axillary lymph nodes are the most commonly affected sites. These increased B-cell lymphocytes eventually spill into the peripheral blood, leading to the detection of lymphocytosis on a CBC.

These neoplastic B cells escape apoptosis and continue to divide over time within the lymph nodes. They then infiltrate the spleen and bone marrow, causing splenomegaly and hypercellular bone marrow (on bone marrow biopsy). The splenomegaly leads to increase sequestration of RBCs and platelets, leading to anemia and thrombocytopenia by decreasing the RBCs and platelets. Patients are more susceptible to autoimmune hemolytic anemia (positive Coombs test) and autoimmune thrombocytopenia. These B cells eventually spread throughout the body, causing systemic symptoms such as fever, night sweats, unintentional weight loss, fatigue, and early satiety. Lack of functional B cells decreases the body's ability to produce antibodies for immune responses, leading to hypogammaglobinemia, which eventually leads to an increased risk of infection.

Skin is the most commonly affected non lymphoid tissue in patients with CLL. Leukemia cutis (skin lesions) mainly involve the face and manifest as papules, macules, plaques, ulcers, blisters, or nodules. A skin biopsy can help confirm the diagnosis of CLL. Nonspecific secondary cutaneous lesions may occur due to bleeding, vasculitis, and infection. Exaggerated reactions to insect bites have been reported in patients as well.

""Chronic lymphocytic leukemia- Pipeline Insight, 2024"" report by DelveInsight outlays comprehensive insights of present scenario and growth prospects across the indication. A detailed picture of the Chronic lymphocytic leukemia pipeline landscape is provided which includes the disease overview and Chronic lymphocytic leukemia treatment guidelines. The assessment part of the report embraces, in depth Chronic lymphocytic leukemia commercial assessment and clinical assessment of the pipeline products under development. In the report, detailed description of the drug is given which includes mechanism of action of the drug, clinical studies, NDA approvals (if any), and product development activities comprising the technology, Chronic lymphocytic leukemia collaborations, licensing, mergers and acquisition, funding, designations and other product related details.

Report Highlights

• The companies and academics are working to assess challenges and seek opportunities that could influence chronic lymphocytic leukemia R&D. The therapies under development are focused on novel approaches to treat/improve chronic lymphocytic leukemia.

Chronic lymphocytic leukemia Emerging Drugs Chapters

This segment of the Chronic lymphocytic leukemia report encloses its detailed analysis of various drugs in different stages of clinical development, including phase II, I, preclinical and Discovery. It also helps to understand clinical trial details, expressive pharmacological action, agreements and collaborations, and the latest news and press releases.

Chronic lymphocytic leukemia Emerging Drugs

• Pirtobrutinib: Loxo Oncology

Pirtobrutinib is an investigational, oral, highly-selective, non-covalent Bruton’s tyrosine kinase (BTK) inhibitor. BTK plays a key role in the B-cell antigen receptor, signaling pathway, which is required for the development, activation and survival of normal white blood cells, known as B-cells, and malignant B-cells. Pirtobrutinib was designed to reversibly bind BTK, deliver consistently high target coverage regardless of BTK turnover rate, preserve activity in the presence of the C481 acquired resistance mutations, and avoid off-target kinases that have complicated the development of both covalent and investigational non-covalent BTK inhibitors.

• Cirmtuzumab: Oncternal Therapeutics

Cirmtuzumab is a first-in-class humanized monoclonal antibody that binds with high affinity to a biologically important epitope on ROR1 (Receptor-tyrosine kinase-like Orphan Receptor 1). ROR1 is a type 1 transmembrane protein, essential for fetal development that is expressed on the plasma membrane with an extracellular domain that is essential for ligand binding and signal transduction. Cirmtuzumab binds to many different types of cancer cells but does not recognize most normal adult tissues. Cirmtuzumab was developed at the University of California in San Diego based on the pioneering scientific research of Thomas Kipps, MD, Ph.D., and his colleagues at the Moores Cancer Center. Oncternal holds an exclusive worldwide license to develop and commercialize antibodies recognizing ROR1. The development of cirmtuzumab has been supported by the California Institute for Regenerative Medicine (CIRM), in recognition of the role of ROR1 in conferring stem cell-like properties to the cancer cells that express it. A Phase II clinical trial is evaluating Cirmtuzumab to treat CLL.

• MS-553: MingSight Pharmaceuticals

MS-553 is a potent, highly selective, oral, non-covalent inhibitor of PKCβ, a signaling molecule immediately downstream of BTK and PLCγ2 in the B-cell receptor (BCR) pathway. As PKCβ is downstream of both BTK and PLCγ2, it has the potential to treat acquired BTK resistance mutations in either protein, a feature absent from many second-generation BTK inhibitors. In the preliminary results, MS-553 was generally well tolerated, with initial anti-tumor activity seen in the heavily pretreated population. Potent to full inhibition of PKCβ signaling over 24 hours of exposure has been demonstrated. Additional dosing of patients will be completed to further assess MS-553 efficacy in patients with acquired resistance mutations in BTK and PLCG2. Currently, the drug is being evaluated in the Phase I/II stage of its development for the treatment of CLL.

• NX-2127: Nurix Therapeutics

NX-2127 is an oral small molecule that combines the activity of a targeted BTK degrader with the cereblon immunomodulatory activity of an IKZF degrader. Cereblon immunomodulatory drugs that induce degradation are IKZF1 and IKZF3. Preclinical data support the activity of NX-2127 in tumor models harboring either wild-type BTK or BTK with mutations conferring clinical resistance to FDA-approved agents. Studies in non-human primates confirm potent BTK degradation with once-daily oral dosing. NX-2127 is being tested in an ongoing Phase I trial for patients with chronic lymphocytic leukemia who have failed prior treatments.

• NX-5948: Nurix Therapeutics

NX-5948 is an oral small molecule degrader of BTK. Preclinical data support the activity of NX-5948 in tumor models harboring either wild-type BTK or BTK with mutations conferring clinical resistance to leading FDA approved agents. NX-5948 lacks cereblon immunomodulatory activity and has demonstrated the ability to cross the blood-brain barrier in animal models. NX-5948 has also demonstrated activity in animal models of autoimmune disease. The drug is currently being evaluated in the Phase I stage of development for the treatment of chronic lymphocytic leukemia.

Further product details are provided in the report……..

Chronic lymphocytic leukemia: Therapeutic Assessment

This segment of the report provides insights about the different Chronic lymphocytic leukemia drugs segregated based on following parameters that define the scope of the report, such as:

• Major Players in Chronic lymphocytic leukemia

There are approx. 55+ key companies which are developing the therapies for chronic lymphocytic leukemia. The companies which have their chronic lymphocytic leukemia drug candidates in the most advanced stage, i.e. phase III include, Loxo Oncology.

• Phases

DelveInsight’s report covers around 60+ products under different phases of clinical development like

• Late stage products (Phase III)
• Mid-stage products (Phase II)
• Early-stage product (Phase I) along with the details of
• Pre-clinical and Discovery stage candidates
• Discontinued & Inactive candidates
• Route of Administration

Chronic lymphocytic leukemia pipeline report provides the therapeutic assessment of the pipeline drugs by the Route of Administration. Products have been categorized under various ROAs such as

• Intravenous
• Subcutaneous
• Oral
• Intramuscular
• Molecule Type

Products have been categorized under various Molecule types such as

• Monoclonal antibody
• Small molecule
• Peptide
• Product Type

Drugs have been categorized under various product types like Mono, Combination and Mono/Combination.

Chronic lymphocytic leukemia: Pipeline Development Activities

The report provides insights into different therapeutic candidates in phase II, I, preclinical and discovery stage. It also analyses Chronic lymphocytic leukemia therapeutic drugs key players involved in developing key drugs.

Pipeline Development Activities

The report covers the detailed information of collaborations, acquisition and merger, licensing along with a thorough therapeutic assessment of emerging chronic lymphocytic leukemia drugs.

Chronic lymphocytic leukemia Report Insights

• Chronic lymphocytic leukemia Pipeline Analysis
• Therapeutic Assessment
• Unmet Needs
• Impact of Drugs

Chronic lymphocytic leukemia Report Assessment

• Pipeline Product Profiles
• Therapeutic Assessment
• Pipeline Assessment
• Inactive drugs assessment
• Unmet Needs

Key Questions

Current Treatment Scenario and Emerging Therapies:

• How many companies are developing chronic lymphocytic leukemia drugs?
• How many chronic lymphocytic leukemia drugs are developed by each company?
• How many emerging drugs are in mid-stage, and late-stage of development for the treatment of chronic lymphocytic leukemia?
• What are the key collaborations (Industry–Industry, Industry–Academia), Mergers and acquisitions, licensing activities related to the chronic lymphocytic leukemia therapeutics?
• What are the recent trends, drug types and novel technologies developed to overcome the limitation of existing therapies?
• What are the clinical studies going on for chronic lymphocytic leukemia and their status?
• What are the key designations that have been granted to the emerging drugs?

Key Players

• Loxo Oncology
• Oncternal Therapeutics
• MingSight Pharmaceuticals
• Nurix Therapeutics
• Starton Therapeutics
• TG therapeutics
• Bristol Myers Squibb
• Novartis
• Aprea Therapeutics
• AstraZeneca
• Genor Biopharma
• Incyte Corporation
• MorphoSys
• Astex Therapeutics
• Lava Therapeutics
• Celgene Corporation

Key Products

• Pirtobrutinib
• Cirmtuzumab
• MS-553
• NX-2127
• NX-5948
• Lenalidomide
• Nivolumab
• Buparlisib
• Ublituximab
• APR-246
• Ceralasertib
• GB261
• MOR00208
• AT7519M
• Buparlisib
• LAVA-051
• JCAR017