Checkpoint Inhibitors - Competitive landscape, 2023

This “Checkpoint inhibitors - Competitive landscape, 2023” report provides comprehensive insights about 180+ companies and 250+ drugs in Checkpoint inhibitors Competitive landscape. It 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

Checkpoint inhibitors: Understanding

Checkpoint inhibitors: Overview

Checkpoint inhibitors are a type of immunotherapy. They block proteins that stop the immune system from attacking the cancer cells. Cancer drugs do not always fit easily into a certain type of treatment. This is because some drugs work in more than one way and belong to more than one group. Checkpoint inhibitors are also described as a type of monoclonal antibody or targeted treatment. The immune system protects humans from disease, killing bacteria and viruses. One main type of immune cell that does this is called a T cell. T cells have proteins on them that turn on an immune response and other proteins that turn it off. These are called checkpoint proteins. Some checkpoint proteins help tell T cells to become active, for example when an infection is present. But if T cells are active for too long, or react to things they shouldn't, they can start to destroy healthy cells and tissues. So other checkpoints help tell T cells to switch off. Some cancer cells make high levels of proteins. These can switch off T cells, when they should really be attacking the cancer cells. So the cancer cells are pushing a stop button on the immune system. And the T cells can no longer recognize and kill cancer cells. Drugs that block checkpoint proteins are called checkpoint inhibitors. They stop the proteins on the cancer cells from pushing the stop button. This turns the immune system back on and the T cells are able to find and attack the cancer cells. These drugs block different checkpoint proteins including: CTLA-4 (cytotoxic T lymphocyte associated protein 4), PD-1 (programmed cell death protein 1), PD-L1 (programmed cell death ligand 1). CTLA-4 and PD-1 are found on T cells. PD-L1 are on cancer cells. These drugs boost all the immune cells, not just the ones that target cancer. So the overactive T cells can cause possible side effects. These might include: tiredness (fatigue), feeling or being sick , dry, itchy skin, skin rash,loss of appetite, diarrhea, breathlessness and a dry cough, caused by inflammation of the lungs. Agents that release these immune brakes have shown activity to recover dysfunctional T cells and regress various cancer. Both cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and Programmed Death-1 (PD-1) play their role as physiologic brakes on unrestrained cytotoxic T effector function. CTLA-4 (CD 152) is a B7/CD28 family; it mediates immunosuppression by indirectly diminishing signaling through the co-stimulatory receptor CD28. Ipilimumab is the first and only FDA-approved CTLA-4 inhibitor; PD-1 is an inhibitory transmembrane protein expressed on T cells, B cells, Natural Killer cells (NKs), and Myeloid-Derived Suppressor Cells (MDSCs). Programmed Death-Ligand 1 (PD-L1) is expressed on the surface of multiple tissue types, including many tumor cells and hematopoietic cells. PD-L2 is more restricted to hematopoietic cells. Blockade of the PD-1 /PDL-1 pathway can enhance anti-tumor T cell reactivity and promotes immune control over the cancerous cells.

Report Highlights

• In April 2023, Enlivex Therapeutics Ltd. announced a clinical collaboration agreement with BeiGene. The Company entered into this collaboration to evaluate the safety and efficacy of Allocetra™, an investigational macrophage-reprogramming cell therapy, in combination with tislelizumab, an anti-PD-1 immune checkpoint inhibitor, for the treatment of patients with advanced-stage solid tumors, a part of the Company's ongoing Phase I/II clinical trial.
• In January 2023, CARsgen Therapeutics Holdings Limited had announced CARsgen's execution of a collaboration agreement with F. Hoffmann-La Roche Ltd to evaluate CARsgen's investigational drug AB011, the first humanized monoclonal antibody against Claudin18.2 (CLDN18.2) that received IND clearance globally, in combination with atezolizumab, Roche's PD-L1 checkpoint inhibitor, along with standard-of-care chemotherapy in patients with gastric or gastroesophageal junction carcinoma . Under the terms of the agreement, Roche will be responsible for operation and conduct of the trial while both companies co-share the costs of the AB011 treatment arms in the study.
• In January 2023, Teon Therapeutics, announced that it has entered into the clinical trial collaboration agreement with Merck. The agreement is for the combination arm of Teon's ongoing, two-armed, open-label, dose escalation and expansion clinical study and will evaluate Teon's oral, immune response modifier, TT-816, in combination with Merck's anti-PD-1 therapy, KEYTRUDA® (pembrolizumab), for patients with advanced solid tumors.
• In October 2022, Immune-Onc Therapeutics, Inc. (“Immune-Onc”), announced it has entered into a clinical trial collaboration and supply agreement with BeiGene to evaluate Immune-Onc's first-in-class myeloid checkpoint inhibitors, IO-108 and IO-202, in combination with BeiGene's anti-PD-1 antibody, tislelizumab, as part of its clinical development programs in China.
• In October 2022, Exelixis, Inc. announced the expansion of its June 2021 Clinical Trial Collaboration and Supply Agreement with Bristol-Myers Squibb Company to include the use of the fixed-dose combination of nivolumab and relatlimab in the ongoing phase 1b STELLAR-002 clinical trial (NCT05176483), which is evaluating XL092 in combination with multiple immune checkpoint inhibitors (ICIs) in advanced solid tumors.

Checkpoint inhibitors: Company and Product Profiles (Marketed Therapies)

1. Company Overview: Merck

At Merck, known as MSD outside of the United States and Canada, are unified around the purpose: Merck use the power of leading-edge science to save and improve lives around the world. For more than 130 years, Merck have brought hope to humanity through the development of important medicines and vaccines. Company aspire to be the premier research-intensive biopharmaceutical company in the world - and today, are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. Merck foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities.

Product Description: Pembrolizumab

Pembrolizumab (Keytruda) is another human IgG4k monoclonal antibody against PD-1. It received its first approval on 4 September 2014, via an accelerated process based on the objective response rate of 24%, from the clinical trial NCT01295827, in metastatic melanoma patients who are refractory to CTLA-4 therapy and BRAF inhibitor if they have BRAF mutation. The FDA further expanded its approval for previously untreated advanced melanoma regardless of BRAF mutation status on 18 December 2015, based on the Keynote-006 trial, a phase 3 randomized trial comparing pembrolizumab against ipilimumab (then standard therapy), which resulted in a prolonged OS and PFS with less toxicity than ipilimumab. Based on Keynote-002, the FDA further expanded its use in ipilimumab refractory advanced Melanoma at the same time as it was shown to be superior to the investigator's choice chemotherapy. On 19 February 2019, the FDA extended the use of pembrolizumab in the adjuvant treatment of lymph node(s)-positive melanoma following complete resection based on the phase 3, EORTC1325/Keynote-054 trial study demonstrating prolonged recurrence-free survival (RFS). Pembrolizumab was approved by the FDA on 2 October 2015 for metastatic NSCLC patients who progressed after platinum-based therapy or EGFR- or ALK-targeted therapy and are positive for PDL-1, via accelerated approval based on the randomized, open-labeled, phase II/III study, Keynote-010 trial, showing improved ORR, PFS, and OS compared to Docetaxel in tumors with at least 1% expression of PDL-1. On 5 August 2016, pembrolizumab was also approved for recurrent or metastatic head and neck squamous cell cancer (HNSCC) patients who progressed on standard platinum-based therapy.

2. Company Overview: Genentech

Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. Merck, a leading science and technology company, operates across life science, healthcare and electronics. More than 64,000 employees work to make a positive difference to millions of people's lives every day by creating more joyful and sustainable ways to live. From providing products and services that accelerate drug development and manufacturing as well as discovering unique ways to treat the most challenging diseases to enabling the intelligence of devices - the company is everywhere. Scientific exploration and responsible entrepreneurship have been key to Merck's technological and scientific advances. This is how Merck has thrived since its founding in 1668. The founding family remains the majority owner of the publicly listed company. Merck holds the global rights to the Merck name and brand. The only exceptions are the United States and Canada, where the business sectors of Merck operate as MilliporeSigma in life science, EMD Serono in healthcare, and EMD Electronics in electronics.

Product Description: Atezolizumab

On 18 May 2016, atezolizumab (Tecentriq) was approved for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) whose disease progressed during or following platinum-containing chemotherapy, or within 12 months of receiving platinum-containing neoadjuvant or adjuvant chemotherapy in the setting of surgical treatment based on the IMvigor210 trial (Category 2A). Later on, atezolizumab received accelerated approval on 17 April 2017 for the treatment of patients with mUC who were not candidates for platinum-based chemotherapy regardless of PD-L1 expression based on the Phase II IMvigor210 study. The FDA issued a statement on 29 June 2018 (similar to pembrolizumab) stating that atezolizumab should be used only for patients whose tumors express PD-L1 ≥ 5% (tumor-infiltrating cells) or who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 expression. On 18 October 2016, the FDA approved atezolizumab for the treatment of people with metastatic non-small-cell lung cancer (NSCLC) with progression on platinum-based chemotherapy, and in progression on targeted therapy in patients with EGFR or ALK abnormalities. This approval is based on two trial results, Phase III OAK and Phase II POPLAR. The FDA approved atezolizumab plus paclitaxel on 8 March 2019 for the treatment of adults with metastatic triple-negative breast cancer in people whose tumors express PD-L1 based on data from the Phase III IMpassion130 study. In December 2022, Genentech, announced that the U.S. Food and Drug Administration (FDA) has approved Tecentriq® (atezolizumab) for the treatment of adult and pediatric patients two years of age and older with unresectable or metastatic alveolar soft part sarcoma (ASPS).

Checkpoint inhibitors: Company and Product Profiles (Pipeline Therapies)

1. Company Overview: BIOCAD

BIOCAD is one of the largest innovative biotech companies in Russia. It brought together world-class R&D centers, modern pharmaceutical and biotechnological production, and preclinical and clinical trials, compliant with international standards. BIOCAD is a full-cycle drug development company, from molecule search to mass production and marketing support. The drugs are intended for the treatment of oncological and autoimmune diseases. Present product portfolio includes 61 medical products, 22 of them are biological. Over 40 products are now in different development stages. Development of drugs for cancer therapy is one of the priorities of the company. There are 2600 people working in BIOCAD, 1/3 of them are researchers and scientists. Offices of the company are located in Brazil, China, Vietnam and UAE.

Product Description: BCD-100

Prolgolimab (BCD-100) is a fully human monoclonal antibody that has specific affinity for the PD-1 receptor. It is an IgG1 immunoglobulin with L234A/L235A mutations which result in lower affinity to Fcγ receptors. It is the first immune checkpoint inhibitor developed in Eastern Europe. Prolgolimab is already approved in Russia for the treatment of unresectable or metastatic melanoma. As part of the Harmony clinical program, prolgolimab is also being developed in combination with other therapies for the treatment of advanced NSCLC and cervical cancer. Currently the drug is in Phase III stage of development for the treatment of Non-Squamous Non-Small Cell Neoplasm of Lung.

2. Company Overview: CanBas Co., Ltd.

CanBas Co., Ltd. is a drug discovery company dedicated to research and development into anticancer agents in the field of immuno-oncology. CanBas possesses a proprietary drug discovery platform enabling in-house development of technologies and products through a combination of basic research and clinical research. As an R&D-based drug discovery company, in principle CanBas conducts early-stage (Phase 1-2) clinical trials internally, then out-licenses drug candidates to pharmaceutical companies for late-stage (Phase 2-3) programs requiring heavy expenditure. CanBas has two major candidate compounds in its pipeline: CBP501 and CBS9106. The company describes the former as an “immune igniter,” while the latter is a reversible XPO1 inhibitor. Although the two have entirely different mechanisms of action, they share an important feature: the ability to selectively kill cancer cells with minimal impact on healthy cells (i.e., effective in reducing side effects), demonstrated both in vivo and in vitro.

Product Description: CBP501

CBP501 is a novel calmodulin-modulating peptide with a well described multimodal anti-tumor mechanism of action. Even with short time exposure treatment, this mode of action leads to increased platinum influx into and cytotoxicity to tumor cells specifically, immunogenic cell death of tumor cells,, suppression of M2 macrophage activity, reduced populations of cancer stem cells, and reduced migration/invasion by and epithelial-to-mesenchymal transition (EMT) of tumor cells. CBP501 also, with cisplatin or carboplatin, enhances the efficacy of several immune checkpoint inhibitors. In the CT-26 syngeneic mice model, use of CBP501 and a platinum agent with anti-PD1, anti-PDL1 or anti-CTLA4, synergistically suppress tumor growth and increases the CD8 T cell and decreases the M2 macrophage at tumor sites. Currently the drug is in Phase II stage of Clinical trial evaluation for the treatment of Pancreatic Cancer Stage IV.

3. Company Overview: BeBetter Med

BeBetter Med is a rapidly-growing novel drug discovery and development company located in Guangzhou, China. It was founded in 2012 by overseas returnees and aims to create advanced novel medicines to treat cancers, autoimmune diseases, metabolic diseases, and other severe diseases. BeBetter Med Inc. possesses strong expertise and outstanding facilities to perform comprehensive pharmaceutical research from drug design and synthesis to clinical development. Currently, ten innovative drug candidates (with independent intellectual property rights) have entered clinical or IND filing stages. Among them, BEBT-908 is in the pivotal phase II trial for the treatment of lymphoma, and has received Breakthrough Therapy designation by the Chinese NMPA. BEBT-209 and BEBT-109 are in the phase III and pivotal phase II trials for the treatment of advanced breast cancer and lung cancer, respectively. A number of new drugs are expected to be launched on the market in the next few years.

Product Description: BEBT-260

BEBT-260 is under development for the treatment of solid tumors including ovarian cancer, breast cancer, non-small cell lung cancer, small-cell lung cancer, head and neck squamous cell carcinoma, colon cancer, cervical cancer, hilar cancer, anal canal cancer, pancreatic cancer, triple-negative breast cancer (TNBC), penile cancer, vulvar cancer, gastric cancer and kidney cancer. The therapeutic candidate acts by targeting Serine/Threonine Protein Kinase Chk1 checkpoint kinase 1 (Chk 1). It is administered through intravenous route. Currently the drug is in Phase I stage of Clinical trial evaluation for the treatment of Solid Tumors.

4. Company Overview: Laekna Therapeutics

Founded in 2016, Laekna is a science-driven, clinical-stage biotechnology company. Laekna has two Core Products and 13 other pipeline product candidates. Core Product LAE002 is an adenosine triphosphate (ATP) competitive AKT inhibitor for the treatment of ovarian cancer, prostate cancer, breast cancer and PD-1/PD-L1 drug-resistant solid tumors. The other Core Product LAE001 is an androgen synthesis inhibitor that simultaneously inhibits cytochrome P450 family 17 subfamily A member 1 (CYP17A1) and cytochrome P450 family 11 subfamily B member 2(CYP11B2) for the treatment of prostate cancer. Laekna has initiated one registrational clinical trial and another five clinical trials for our Core Products LAE002 and LAE001. Among these six clinical trials, three are multi-regional clinical trials (MRCTs) designed to address medical needs in the standard of care (SOC)-resistant cancers. As of the Latest Practicable Date, Laekna owned 163 patents and patent applications (including in-licensed patents and patent applications with global rights). Laekna's internal drug discovery primarily focuses on identifying innovative immunology therapies for cancer and liver fibrosis.

Product Description: FAZ053

FAZ053 (anti-PD-L1) is an investigational immuno-oncology treatment being developed by Laekna Therapeutics for patients with advanced cancers. It is a monoclonal antibody directed against a protein called programmed cell death-1 ligand 1 (PD-L1). Upon administration, anti-PD-L1 monoclonal antibody FAZ053 binds to PD-L1, blocking its binding to and activation of its receptor programmed death 1 (PD-1), which may enhance the T-cell-mediated anti-tumor immune response and reverse T-cell inactivation. Laekna plans to start trials on combination therapies as soon as possible in order to address the unmet needs of people with cancer and bring innovative, effective treatments to more cancer patients across China.

Checkpoint inhibitors Analytical Perspective

In-depth Commercial Assessment: Checkpoint inhibitors Collaboration Analysis by Companies

The Report provides in-depth commercial assessment of drugs that have been included, which comprises collaboration, agreement, licensing and acquisition - deals values trends. The sub-segmentation is described in the report which provide company-company collaboration (licensing/partnering), company academic collaboration and acquisition analysis in tabulated form.

• Checkpoint inhibitors Competitive Landscape

The report comprises of comparative assessment of Companies (by therapy, development stage, and technology).

Checkpoint inhibitors Report Assessment

• Company Analysis
• Therapeutic Assessment
• Pipeline Assessment
• Inactive drugs assessment
• Unmet Needs

Key Questions Answered

Current Treatment Scenario and Emerging Therapies:

• How many companies are developing Checkpoint inhibitors drugs?
• How many Checkpoint inhibitors drugs are developed by each company?
• How many emerging drugs are in mid-stage, and late-stage of development for the treatment of Checkpoint inhibitors?
• What are the key collaborations (Industry-Industry, Industry-Academia), Mergers and acquisitions, licensing activities related to the Checkpoint inhibitors 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 Checkpoint inhibitors and their status?
• What are the key designations that have been granted to the emerging and approved drugs?

Key Players

• BeBetter Med
• BIOCAD
• CanBas Co., Ltd.
• Laekna Therapeutics
• Genentech
• Alphamab Oncology
• Hangzhou Sumgen Biotech
• Harbour BioMed
• Aurigene Discovery Technologies
• BeiGene
• Apollomics
• BCN Biosciences
• Phio Pharmaceuticals
• Atridia
• Jiangsu HengRui Medicine
• EMD Serono
• Innovent Biologics
• Agenus
• Eucure Biopharma

Key Products

• BCD-100
• CBP501
• BEBT-260
• FAZ053
• TECENTRIQ
• Envafolimab
• Durvalumab
• SG 12473
• HBM-9027
• CA-170
• Tislelizumab
• Geptanolimab
• BCN 176
• PH-3861
• Adebrelimab
• M7824
• IBI-310
• AGEN-1181
• YH-001

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