Graft versus host disease - Pipeline Insight, 2023

DelveInsight's , "Graft versus host disease - Pipeline Insight, 2023" report provides comprehensive insights about 60+ companies and 65+ pipeline drugs in Graft versus host disease 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

Graft versus host disease: Understanding

Graft versus host disease: Overview

Graft-versus-host disease (GvHD) is a systemic disorder that occurs when the graft's immune cells recognize the host as foreign and attack the recipient's body cells. "Graft" refers to transplanted, or donated tissue, and "host" refers to the tissues of the recipient. It is a common complication after allogeneic hematopoietic stem cell transplant (HCT). GvHD has been classically classified based on the timing of presentation into acute and chronic using a cutoff of 100 days post-transplant. This has been further subclassified based on clinical manifestations accepted by the NIH into: 1) Acute classic GvHD: Presents within 100 days of transplantation with classical clinical features of acute GvHD. 2) Persistent, recurrent, or late-onset acute GvHD: Manifests with clinical features of classic acute GvHD but after 100 days of transplantation. 3) Classic chronic GvHD: Presents after 100 days of transplant with classic clinical features of chronic GvHD. and 4) Overlap syndrome: May present at any time post-transplant with features of both acute and chronic GvHD

Cells of the immune system are trained early to differentiate between "self" cells and "non-self" cells. The ability to recognize "non-self" cells depends on a set of genes knows as the histocompatibility genes that provide instructions for making a group of related proteins known as major histocompatibility complex (MHC proteins) or human leukocyte antigens (HLA). The histocompatibility genes code for MHC class I proteins that are present on all nucleated cells in the body and MHC class II molecules that are expressed only on antigen-presenting cells. During transplantation, the donor tissue is usually obtained from a genetically different individual known as an "allograft". Immune cells in the graft recognize the MHC proteins of the recipient tissue as "non-self" and triggers an immune response between the donor and the recipient.

All patients receiving HCT should undergo prophylactic treatment for GvHD. Treatment protocols differ by institution, but most commonly use a combination of cyclosporine and methotrexate is continued for several months post-transplantation. Antibacterial, antiviral, and antifungal prophylaxis is typically added post HCT to mitigate the risk of infections. Treatment for GvHD depends on the severity of symptoms and organs involved. Most treatment options focus on immunosuppression of donor T cells and must be balanced to reduce the symptoms of GvHD while avoiding decreasing the beneficial graft vs. tumor (GVT) response. Corticosteroids remain the most commonly used treatment. Grade 1 GvHD is usually managed with topical steroids in an attempt to control local symptoms. Topical tacrolimus is an option for steroid-resistant disease. Grade 2 or higher requires the addition of systemic steroids, most commonly methylprednisolone 2 mg/kg/day in divided doses. In cases of GI involvement, the addition of a nonabsorbable corticosteroid (budesonide or beclomethasone) is more effective than systemic treatment alone. Steroids should be avoided if a GI infection is present. Gradual tapering of the steroid over the course of several months is important to prevent a GvHD flare. Patients with chronic GvHD will typically require prolonged courses of steroids, generally 2 - 3 years. Some patients may require lifelong treatment. Octreotide can be added in an attempt to decrease the amount of diarrhea. The addition of other agents to steroids include mycophenolate, etanercept, pentostatin, monoclonal antibodies, sirolimus, alpha-1-antitrypsin, mesenchymal stromal cells, and extracorporeal photopheresis. However, their efficacy is unclear. Cyclosporine can be added to the treatment regimen for chronic GvHD in an attempt to decrease steroid dosage and duration.

"Graft versus host disease- Pipeline Insight, 2023" report by DelveInsight outlays comprehensive insights of present scenario and growth prospects across the indication. A detailed picture of the Graft versus host disease pipeline landscape is provided which includes the disease overview and Graft versus host disease treatment guidelines. The assessment part of the report embraces, in depth Graft versus host disease 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, Graft versus host disease 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 Graft versus host disease R&D. The therapies under development are focused on novel approaches to treat/improve Graft versus host disease.

Graft versus host disease Emerging Drugs Chapters

This segment of the Graft versus host disease 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.

Graft versus host disease Emerging Drugs

MaaT013: MaaT Pharma

MaaT Pharma is developing MaaT013, which is made up of allogeneic, full-ecosystem pooled bio therapeutic intestinal micro biota manufactured in France, per the GMP requirements. It is an off-the-shelf, standardized, pooled-donor, high-richness micro biome bio therapeutic in enema formulation. The product is characterized by a high diversity and consistent richness of microbial species. MaaT013 aims to restore the symbiotic relationship between the patient's functional gut micro biome and their immune system to correct the responsiveness and tolerance of immune functions and thus reduce steroid-resistant, gastrointestinal-predominant aGvHD. In previous studies, MaaT013 showed interesting results; therefore, warranted as salvage therapy in steroid and JAK inhibitors-resistant GI-aGvHD patients. The drug has been granted Orphan Drug Designation by the US FDA and the European Medicines Agency (EMA). MaaT013 is currently being investigated in a pivotal Phase III trial (ARES) in patients with acute Graft-versus-Host-Disease with gastrointestinal involvement (GI-aGvHD) who are refractory to both steroids, the standard of care first-line treatment, and to ruxolitinib used as a second-line treatment.

MC0518: Medac

Obnitix, also called MC0518, is a new special preparation of mesenchymal stromal cells (MSC) produced with the help of an innovative process by Medac. Obnitix is administered via an infusion. The administration of Obnitix, which uses mononuclear cells from the bone marrow of at least eight donors, activates a suppression of pro-inflammatory messenger substances and T-cell suppression. The new method has made it possible to obtain a uniform and reproducible product with stable batch production. Currently, the drug is in the Phase III stage of its development for the treatment of Graft versus host disease.

SNDX-6532: Syndax Pharmaceutical

Axatilimab (SNDX-6352) is an investigational high-affinity antibody targeting the colony-stimulating factor 1 receptor (CSF-1R). CSF-1R signaling has been demonstrated in nonclinical studies to be a key regulatory pathway involved in the expansion and infiltration of donor-derived macrophages that mediate the disease processes involved in cGvHD. The company believes that CSF-1R blockade with axatilimab (SNDX-6352) may reduce the number of these pro-inflammatory macrophages and play a vital role in treating cGvHD. As of now, an ongoing Phase II (NCT04710576, AGAVE-201) study will assess the efficacy, protection, and tolerability of axatilimab, a CSF-1R inhibitor, at three different dose levels in patients with persistent or refractory active cGvHD who have undergone at least two prior lines of systemic therapy due to disease progression, intolerance, or toxicity.

Neihulizumab: AltruBio

Neihulizumab/ALTB-168 is a humanized therapeutic antibody with a unique mechanism of action, preferentially inducing apoptosis of late-stage activated T cells. This novel activated-T cell apoptosis-inducing antibody effectively eliminates chronic pathogenic T cells while fully maintaining host defense, leading to durable clinical efficacy without increasing the risk of infection or cancer.These two characteristics, which have been well demonstrated in our proof of concept clinical studies, offer a sustainable competitive advantage over existing therapies. Currently, the drug is in the Phase I stage of its development for the treatment of Graft versus host disease.

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

Graft versus host disease: Therapeutic Assessment

This segment of the report provides insights about the different Graft versus host disease drugs segregated based on following parameters that define the scope of the report, such as:

• Major Players in Graft versus host disease
• There are approx. 60+ key companies which are developing the therapies for Graft versus host disease. The companies which have their Graft versus host disease drug candidates in the most advanced stage, i.e. phase III include, MaaT Pharma.
• Phases

DelveInsight's report covers around 65+ 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

"Graft versus host disease pipeline report" provides the therapeutic assessment of the pipeline drugs by the Route of Administration. Products have been categorized under various ROAs such as

• Oral
• Intravenous
• Subcutaneous
• Parenteral
• Topical
• Molecule Type

Products have been categorized under various Molecule types such as:

• Recombinant fusion proteins
• Small molecule
• Monoclonal antibody
• Peptide
• Polymer
• Gene therapy
• Product Type

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

Graft versus host disease: Pipeline Development Activities

The report provides insights into different therapeutic candidates in phase II, I, preclinical and discovery stage. It also analyses Graft versus host disease 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 Graft versus host disease drugs.

Graft versus host disease Report Insights

• Graft versus host disease Pipeline Analysis
• Therapeutic Assessment
• Unmet Needs
• Impact of Drugs

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

Key Players

• AltruBio
• Syndax Pharmaceutical
• MaaT Pharma
• Medac
• CSL Behring
• Takeda
• Oncoimmue
• ElsaLys Biotech
• Xenikos
• Incyte Corporation
• Jazz Pharmaceutials
• Kadmon Corporation
• Regimmune Corporation
• Medsenic
• AstraZeneca
• Biogen
• Pfizer
• Equillium
• GlaxoSmithKline
• Amgen
• CTI BioPharma
• Bristol-Myers Squibb
• Synthetic Biologics
• Evive Biotech
• Orca Bio
• Novartis
• Roche
• Millennium

Key Products

• MaaT013
• MC0518
• SNDX-6532
• Neihulizumab
• CSL 964 Alpha-1 antitrypsin
• Entyvio
• MK-7110
• Leukotac
• T-Guard
• Itacitinib
• Defitelio
• KD025
• RGI-2001
• Arscimed
• Calquence
• Tysabri
• Ninlaro
• Gazyva
• Farydak
• Orencia
• SYN-004
• Orca-T
• F-652
• EQ001
• Pacritinib
• Efavaleukin Alfa
• Daurismo
• Benlysta