Gene Therapy-Competitive landscape, 2023

This “Gene Therapy - Competitive landscape, 2023” report provides comprehensive insights about 250+ companies and 300+ drugs in Gene Therapy 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

Gene Therapy: Understanding

Gene Therapy: Overview

Gene therapy is a technique that uses a gene(s) to treat, prevent or cure a disease or medical disorder. Often, gene therapy works by adding new copies of a gene that is broken, or by replacing a defective or missing gene in a patient's cells with a healthy version of that gene. Both inherited genetic diseases (e.g., hemophilia and sickle cell disease) and acquired disorders (e.g., leukemia) have been treated with gene therapy.

Gene therapy is the use of genetic material to treat or prevent disease. The genetic material that is delivered, DNA or RNA, has instructions to change how a protein - or group of proteins - is produced by the cell. For some diseases, this means making changes to account for too much, not enough, or incorrect essential proteins being produced within cells. This new genetic material, such as a working gene, is delivered into the cell using a vector. A vector is like a package used to deliver a specific message. Viruses can be used as vectors because they have evolved to be very good at getting into cells. Scientists have learned how to remove the viral genes and use this same ability to treat or prevent disease. In this case, their goal is to insert the new genetic material into the cell. All viral vectors are tested many times for safety prior to being used in humans.

The vector can be delivered in one of two ways:

• Ex-vivo treatment removes the person's own cells and delivers the genetic material to these cells outside the body. The modified cells are then returned to the body.
• In-vivo treatment means the genetic material is delivered directly into the person, such as through an injection

Gene therapies can work by several mechanisms:

• Replacing a disease-causing gene with a healthy copy of the gene
• Inactivating a disease-causing gene that is not functioning properly
• Introducing a new or modified gene into the body to help treat a disease
• Gene therapy products are being studied to treat diseases including cancer, genetic diseases, and infectious diseases.

There are a variety of types of gene therapy products, including:

• Plasmid DNA: Circular DNA molecules can be genetically engineered to carry therapeutic genes into human cells.
• Viral vectors: Viruses have a natural ability to deliver genetic material into cells, and therefore some gene therapy products are derived from viruses. Once viruses have been modified to remove their ability to cause infectious disease, these modified viruses can be used as vectors (vehicles) to carry therapeutic genes into human cells.
• Bacterial vectors: Bacteria can be modified to prevent them from causing infectious disease and then used as vectors (vehicles) to carry therapeutic genes into human tissues.
• Human gene editing technology: The goals of gene editing are to disrupt harmful genes or to repair mutated genes.
• Patient-derived cellular gene therapy products: Cells are removed from the patient, genetically modified (often using a viral vector) and then returned to the patient.

Report Highlights

• In June 2022, Transgene and BioInvent International announced a clinical trial collaboration and supply agreement with MSD, a tradename of Merck & Co to evaluate the Gene Therapy BT-001 in combination with MSD's anti-PD-1 therapy KEYTRUDA (pembrolizumab) in a Phase I/IIa clinical trial for the treatment of patients with solid tumors.
• In April 2022, ImmVira announced that, company had reached a cooperation agreement with Roche to establish clinical research partnership recently, to conduct clinical studies in the U.S. on the combination therapy of ImmVira's MVR-T3011 IT and Roche's MEK inhibitor cobimetinib, to evaluate the safety and efficacy of this combo strategy.
• In March 2022, Targovax announced a collaboration with Agenus to utilize their proprietary vaccine adjuvant QS-21 STIMULON as an immune-stimulatory component of the TG vaccines for future development and commercialization.
• In February 2022, Calidi Biotherapeutics, Inc. and Edoc Acquisition Corp. organized to acquire or merge with one or more businesses, have entered into a definitive merger agreement. Upon closing the transaction, anticipated to occur in the second quarter of 2022, the combined company will be named Calidi Biotherapeutics, Inc. and led by Allan Camaisa, CEO and Chairman of the Board. In addition, the combined company's common stock intends to list on the Nasdaq Capital Market.
• In January 2022, Transgene and PersonGen BioTherapeutics announced a strategic collaboration to evaluate the feasibility and efficacy of combination therapy associating PersonGen's TAA06 CAR-T cell injection with intravenous (IV) administration of an armed Gene Therapy, from Transgene's Invir.IO™ platform, in solid tumors including pancreatic cancer and brain glioma. The collaboration aimed to demonstrate the combination's likely synergistic mechanisms to potentiate CAR-T cell therapy. Under the terms of the collaboration agreement, Transgene to develop multiple new OV candidates, using its patented Gene Therapy backbone VVcopTK-RR- and its Invir.IO™ technology platform, specifically for IV administration in combination with PersonGen's TAA06 CAR-T injection. PersonGen to evaluate the efficacy of the combination to eliminate solid tumors in preclinical models.

Gene Therapy: Company and Product Profiles (Marketed Therapies)

1. Company Overview: Juno Therapeutics, Inc./Bristol-Myers Squibb

Juno is a clinical-stage company that brings together three of the world's leading cancer centers - Fred Hutchinson Cancer Research Center, Memorial Sloan-Kettering Cancer Center and Seattle Children's Research Institute - in unique partnership to advance a broad pipeline of breakthrough immunotherapies. On January 22, 2018, Juno Therapeutics was acquired by biotechnology company Celgene for $9 billion. In November 2019, Bristol-Myers Squibb (BMS) announced that it has completed its acquisition of Celgene.

Product Description: BREYANZI

BREYANZI (lisocabtagene maraleucel) is a CD19-directed genetically modified autologous T cell immunotherapy administered as a defined composition of CAR-positive viable T cells (consisting of CD8 and CD4 components). The CAR is comprised of the FMC63 monoclonal antibody-derived single-chain variable fragment (scFv), IgG4 hinge region, CD28 transmembrane domain, 4-1BB (CD137) costimulatory domain, and CD3 zeta activation domain.

On February 5, 2021, the Food and Drug Administration approved lisocabtagene maraleucel (Breyanzi, Juno Therapeutics, Inc.) for the treatment of adult patients with relapsed or refractory (R/R) large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B.

2. Company Overview: BioMarin Pharmaceutical Inc.

Founded in 1997, BioMarin is a global biotechnology company dedicated to transforming lives through genetic discovery. The company develops and commercializes targeted therapies that address the root cause of the genetic conditions. BioMarin's unparalleled research and development capabilities have resulted in eight transformational commercial therapies for patients with rare genetic disorders. The company's distinctive approach to drug discovery has produced a diverse pipeline of commercial, clinical, and pre-clinical candidates that address a significant unmet medical need, have well-understood biology, and provide an opportunity to be first-to-market or offer a substantial benefit over existing treatment options.

Product Description: Valoctocogene Roxaparvovec

Valoctocogene roxaparvovec is an investigational AAV5 gene therapy for the treatment of severe hemophilia A. It was approved for conditional use in the European Union August 24, 2022 and marketed as ROCTAVIAN™ (valoctocogene roxaparvovec). It is not approved for use in the United States.

In March 2023, BioMarin Pharmaceutical Inc. received notice from the U.S. Food and Drug Administration (FDA) that the agency has extended review of the company's Biologics License Application (BLA) for ROCTAVIAN™ (valoctocogene roxaparvovec) gene therapy for adults with severe hemophilia A.

The FDA determined that the submission of the three-year data analysis from the ongoing Phase 3 GENEr8-1 study constituted a Major Amendment due to the substantial amount of additional data and set a new PDUFA Target Action Date of June 30, 2023. Additionally, the FDA granted Regenerative Medicine Advanced Therapy (RMAT) designation to valoctocogene roxaparvovec in March 2021. The RMAT designation is complementary to Breakthrough Therapy designation, which the company received for valoctocogene roxaparvovec in 2017. BioMarin's valoctocogene roxaparvovec also received Orphan Drug designation from the European Medicines Agency (EMA) and FDA for the treatment of severe hemophilia A.

Gene Therapy: Company and Product Profiles (Pipeline Therapies)

1. Company Overview: Candel Therapeutics

Candel is a late clinical stage biopharmaceutical company focused on helping patients fight cancer with oncolytic viral immunotherapies. Candel's engineered viruses are designed to induce immunogenic cell death through direct viral-mediated cytotoxicity in cancer cells, thus releasing tumor neo-antigens and creating a pro-inflammatory microenvironment at the site of injection. Candel has established two oncolytic viral immunotherapy platforms based on novel, genetically modified adenovirus and herpes simplex virus (HSV) constructs. CAN-2409 is the lead product candidate from the adenovirus platform and CAN-3110 is the lead product candidate from the HSV platform. New discovery programs are based on the HSV platform.

Product Description: CAN-2409

CAN-2409, Candel's most advanced oncolytic viral immunotherapy product candidate, is a replication-deficient adenoviral gene construct encoding the herpes simplex virus thymidine kinase (HSV-tk) gene. HSV-tk is an enzyme that locally converts orally administered valacyclovir into a toxic metabolite that kills nearby cancer cells. Intra-tumoral administration results in immunogenic cell death, followed by the release of tumor-specific neoantigens in the tumor microenvironment. At the same time, the adenoviral vector elicits a strong pro-inflammatory signal to the tumor microenvironment, creating the optimal conditions to induce a specific CD8+ cytotoxic T cell-mediated immune response against the injected tumor and the uninjected distant metastases. This dual mechanism of antigen unmasking and immune activation may enable CAN-2409 to generate a powerful and lasting attack against a variety of the patient's tumor-associated neoantigens, minimizing the possibility for immune escape and development of tolerance. Because of its versatility, CAN-2409 may have the potential to treat a broad range of solid tumors. Encouraging activity has been shown in several preclinical and clinical settings as monotherapy as well as in in combination with standard of care radiation therapy, surgery, chemotherapy, and immune checkpoint inhibitor treatment. Currently the product is in Phase III stage of development for the treatment of Prostate Cancer.

2. Company Overview: CRISPR Therapeutics

CRISPR Therapeutics is a leading gene editing company focused on developing transformative gene-based medicines for serious diseases using its proprietary CRISPR/Cas9 platform. CRISPR/Cas9 is a revolutionary gene editing technology that allows for precise, directed changes to genomic DNA. CRISPR Therapeutics has established a portfolio of therapeutic programs across a broad range of disease areas including hemoglobinopathies, oncology, regenerative medicine and rare diseases. To accelerate and expand its efforts, CRISPR Therapeutics has established strategic partnerships with leading companies including Bayer, Vertex Pharmaceuticals and ViaCyte, Inc. CRISPR Therapeutics AG is headquartered in Zug, Switzerland, with its wholly-owned U.S. subsidiary, CRISPR Therapeutics, Inc., and R&D operations based in Boston, Massachusetts, and business offices in San Francisco, California and London, United Kingdom.

Product Description: CTX001

CTX001™, is an investigational, autologous, ex vivo CRISPR/Cas9 gene-edited therapy that is being evaluated for patients with TDT or SCD characterized by recurrent VOCs, in which a patient's own hematopoietic stem cells are edited to produce high levels of fetal hemoglobin (HbF; hemoglobin F) in red blood cells. HbF is the form of the oxygen-carrying hemoglobin that is naturally present during fetal development, which then switches to the adult form of hemoglobin after birth. The elevation of HbF by exa-cel has the potential to alleviate transfusion requirements for patients with TDT and reduce painful and debilitating sickle crises for patients with SCD. The drug is currently investigated in B-cell malignancies in Phase I/II trial.

3. Company Overview: TILT Biotherapeutics

TILT Biotherapeutics is a clinical-stage biotechnology company developing cancer therapeutics based on its proprietary oncolytic adenoviruses armed with molecules including cytokines that can stimulate, or suppress, T cells. The company's patented TILT® technology, which can be delivered locally and systemically, modifies the tumor microenvironment, and eliminates its ability to suppress immune responses to cancer, thereby enhancing T-cell therapies such as immune checkpoint inhibitors, tumor infiltrating lymphocyte (TIL) therapy, and CAR T therapies. TILT's lead asset, TILT-123, is a 5/3 chimeric serotype adenovirus armed with two human cytokines: TNF alpha and IL-2. TILT-123 has demonstrated a 100% response rate in pre-clinical cancer models in vivo, and it is currently in Phase I clinical trials.

Product Description: TILT-123

TILT-123 is the result of years of engineering and testing of ten prototype Gene Therapy Cancer Therapyes in almost 300 patients in the Advanced Therapy Access Program (ATAP) at the University of Helsinki, Finland. It is optimized to generate an anti-cancer immune response by boosting the activity of T-cells and also stimulating other arms of the innate and adaptive immune system. TILT-123 is a human 5/3 chimeric adenovirus that has been engineered for targeting, safety and potency. The viral construct includes double selectivity (E2F promoter and D24 deletion in the E1A gene), which means that replication and transgene production are only possible in cancer cells which are uncontrollably dividing and have a high expression of E2F. This is an important safety feature, ensuring that the therapeutic effect is targeted only at cancer cells. TILT-123 can be administered by intravenous, intratumoral, intraperitoneal and intrapleural injection.

4. Company Overview: Akamis Bio

Akamis Bio is a clinical-stage oncology company whose mission is to leverage its groundbreaking Tumor-Specific Immuno-Gene Therapy (T-SIGn) platform to positively impact the lives of people living with cancer. To achieve that mission, the company is developing a portfolio of solid tumor-targeted T-SIGn therapeutics which aim to enable a patient's own immune system to recognize, attack, and clear their cancer. Akamis Bio has a growing pipeline of T-SIGn therapeutics anchored by our two clinical stage programs, NG-350A and NG-641. We have an extensive and growing body of clinical experience with T-SIGn® therapeutics with more than 200 patients treated across both the monotherapy setting, as well as in combination with checkpoint inhibitors. Across our clinical studies, T-SIGn therapeutics have demonstrated a consistent safety & tolerability profile, as well as promising preliminary evidence of clinical activity.

Product Description: NG-347

NG-347 is armed with three transgenes: secreted interferon-α (IFNα), secreted macrophage inflammatory protein-α (MIP1α) and membrane-bound CD80. NG-347 allows IFNα to be expressed directly within the tumor, bypassing the STING pathway. Membrane bound CD80 acts as a costimulatory ligand to enhance T cell activation. KLS 3021 candidate is progressing through preclinical studies in readiness for entering clinical trials.

Gene Therapy Analytical Perspective

In-depth Commercial Assessment: Gene Therapy 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.

Gene Therapy Competitive Landscape

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

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

Key Players

• Candel Therapeutics
• SillaJen Biotherapeutics
• Wuhan Binhui Biotechnology
• Virogin Biotech
• Replimune
• Istari Oncology
• Immvira Pharma
• Lokon Pharma
• ORCA Therapeutics
• Beijing SyngenTech
• Tasly Pharmaceuticals
• Turnstone Biologics
• BioInvent
• Transgene
• Elicera Therapeutics
• Orgenesis
• Virttu Biologics
• Imugene
• Astellas Pharma
• Mustang Bio
• Virogin Biotech
• Memgen
• Replimune
• Immvira Pharma
• PsiOxus Therapeutics
• VCN Biosciences
• Candel therapeutics
• Sorrento Therapeutics
• Imugene Limited
• Calidi Biotherapeutics
• Replimune
• TILT Biotherapeutics
• DNAtrix

Key Products

• CAN-2409
• Pexa-Vec
• OH 2
• VG161
• RP1
• Lerapolturev
• Voyager V1
• ONCOS 102
• LOAd 703
• ORCA-010
• SynOV1.1
• T601
• RIVAL-01
• BT-001
• TG 6002
• ELC-100
• AloCelyvir
• HSV1716
• CHECKVacc
• ASP9801
• MB-108
• NNV-1
• VG 201
• MEM 288
• RP2
• MVR-C5252
• NG-641
• MV-NIS
• NG-350A
• VCN-01
• CAN-3110
• STI-1386
• VAXINIA
• NNV 2
• RP3
• TILT-123
• DNX-2440