Large unmet needs for autoimmune disease therapeutics remain. For many patients, including approximately 25% of those with graft versus host disease (GvHD), existing therapeutics are inadequate. The outlook for better ones, though, is increasingly hopeful.
In December, the U.S. Food & Drug Administration (FDA), in a first, approved a mesenchymal stem cell (MSC) therapeutic for children and adolescents with steroid-refractory acute GvHD. This action opens the door to follow-on indications with excessive inflammation, such as inflammatory bowel disease (IBD) and psoriasis.
In bone marrow transplants, bone marrow cells typically are harvested from donors and grafted into patients. Sometimes, however, the bone marrow rejects its new host, resulting in GvHD. While donor cells certainly address a need, they are not a panacea.
An alternative therapeutic approach to control GvHD is needed, especially for patients who fail first-line therapy. Kiji Therapeutics is developing one such strategy by engineering MSCs for enhanced potency and tighter targeting.
The approach used by Kiji Therapeutics transduces mesenchymal stem cells and induced pluripotent stem cells with the genes encoding interleukin-10 (IL-10) to regulate the immune system and C-X-C Chemokine Receptor 4 (CXCR4) to improve targeting.
Compared to wild type mesenchymal stem cells (WT-MSC) that are merely collected and expanded, “these cells are engineered to be more potent, more targeted, and [to enhance] the therapeutic benefit,” Miguel Forte, MD, PhD, CEO of Kiji Therapeutics and chair of the International Society for Cell & Gene Therapy, tells GEN. Animal studies to date suggest they are approximately 70% more effective, “but we will have to confirm that in clinical trials,” Forte says.
Kiji’s CEO, Miguel Forte, MD, PhD, is exploring inter-actions with larger companies with complementary products to help advance his company’s MSC and iPSC products toward commercialization.
Preclinical studies in NSG mice to compare Kiji’s therapeutic to WT-MSC treatment showed, at 21 days, that the CXCR4/IL-10 treated mice had gained approximately five percent of their body weight and had a GvHD score of one. The WT-MSC-treated mice, in contrast, lost approximately three percent of their body weight and had a GvHD score of four. Similarly notable effects were seen in IBD, with 80% of mice experiencing a long-term (16-day) response, suggesting the potential therapeutic may positively affect the innate immune system.
Forte says he expects manufacturing these engineered cells to be straightforward. Their first-generation manufacturing system already can produce an off-the-shelf product for clinical trials, using donor cells that are expanded and engineered. “That gives us enough cells and a reasonable cost of goods, with a value proposition that will enable us to take [some eventual] third-generation product to the market,” Forte says.
The second generation of manufacturing, expected in about 24 months, however, will use an iPSC cell line rather than donor cells, he says. This will ensure greater consistency and scalability, less cost, and, Forte says, “the ability to deliver large quantities of product at a very attractive value proposition.”
Last autumn, Kiji announced a planned merger with REGiMMUNE, a Taiwanese company. That plan has since been halted and the two will continue their development independently.
That doesn’t mean other collaborations are off the table. Forte says he plans to continue establishing the data and, about midway in the clinical development process, would welcome a big pharma partner with a complementary product portfolio. Currently, he says, “We continue to explore interactions in Taiwan and with other companies.”
Since Kiji’s market is physicians (i.e., hematologists, gastroenterologists, and–for future psoriasis indications–rheumatologists and dermatologists), it would be mutually advantageous to partner with a company that already has first-line products in these indications along with an existing sales force. Such a partnership, Forte points out, would allow the larger company to not only present its own, first-line therapeutic, but to also be able to present a second-line therapeutic–Kiji’s–for patients who need an alternative.
The company is open to licensing or acquisition discussions to advance these emerging therapeutics to commercialization. The more immediate plan, however, is to develop access to the necessary technologies, team, and funding for clinical development. To do this, “We’re actively pursuing interactions with venture capitalists,” Forte says. “The subsequent challenge is to put the value that we generate in the clinic in the right position vis-à-vis the competition, clinical needs, and patient and physician needs.”
The projects that most capture Forte’s imagination, he says, are those with interesting scientific questions, development potential, and a value proposition that can return patients to normal lives. That makes IBD particularly interesting to him.
“IBD is a condition that is still very limiting for patients,” Forte points out. “These are normally young, active people who have problems that limit their social lives… work lives… private lives.”
While the IBD population shares multiple characteristics, “Recent publications have shone there is one phenotype that depends on one aggressive cell–the macrophage. Those macrophage-dependent patients can be identified by their genetic profile,” Forte says.
“What we’ve seen in preclinical data is that we’re able to control the models of IBD and, in particular, we’re able to switch the activity of those aggressive cells. I would like to confirm that, expand that, and [develop] a very strong, targeted mechanism of action and defined value proposition for those patients.”
That combination of interesting science, development potential, and the ability to make a positive difference in patients’ lives is, in fact, what drew Forte to Kiji.
Forte came across this technology when a Parisian venture capital group asked him to conduct due diligence on a technology in Madrid. As Forte recollects, “I did my report, saying this is exciting and brings value to patients. It’s really what cell therapy is about, using the cell function optimized by gene editing.
“They said, ‘Would you like to join us and fund the company?’” He did, and Kiji Therapeutics was formed in early 2023.
The name, Kiji, was intended to be inspirational and connote a sense of renewal. It also needed to reflect the company’s Spanish and French roots. “We identified an island (uninhabited) in the Bidasoa River between France and Spain, called Pheasant Island,” he recalls. Its governance alternates between the two countries every six months.
“But, ‘pheasant’ is not a great name for a biotech, so we looked around. In Japanese, ‘kiji’ means pheasant as well as ‘phoenix.’” That chosen name, therefore, connotes not only a bridge between France and Spain but the hope of renewal.
The young company, headquartered in Paris, still collaborates with the Madrid research group. With manufacturing issues ironed out and materials ready to submit to regulators, “We aim to be in the clinic by the end of this year or early next year,” Forte says.
Location: 4 Rue Thenard, Paris 05, France
Contact: [email protected]
Website: kiji-tx.com
Principal: Miguel Forte, MD, PhD, CEO
Number of Employees: 4
Focus: A pre-clinical company developing genetically engineered mesenchymal stem cell and induced pluripotent stem cel therapies for inflammatory diseases.
The post Bridging Technologies Renew Hope for Treating Inflammatory Diseases appeared first on GEN - Genetic Engineering and Biotechnology News.
In December, the U.S. Food & Drug Administration (FDA), in a first, approved a mesenchymal stem cell (MSC) therapeutic for children and adolescents with steroid-refractory acute GvHD. This action opens the door to follow-on indications with excessive inflammation, such as inflammatory bowel disease (IBD) and psoriasis.
In bone marrow transplants, bone marrow cells typically are harvested from donors and grafted into patients. Sometimes, however, the bone marrow rejects its new host, resulting in GvHD. While donor cells certainly address a need, they are not a panacea.
An alternative therapeutic approach to control GvHD is needed, especially for patients who fail first-line therapy. Kiji Therapeutics is developing one such strategy by engineering MSCs for enhanced potency and tighter targeting.
IL-10 and CXCR4 boost treatment efficacy
The approach used by Kiji Therapeutics transduces mesenchymal stem cells and induced pluripotent stem cells with the genes encoding interleukin-10 (IL-10) to regulate the immune system and C-X-C Chemokine Receptor 4 (CXCR4) to improve targeting.
Compared to wild type mesenchymal stem cells (WT-MSC) that are merely collected and expanded, “these cells are engineered to be more potent, more targeted, and [to enhance] the therapeutic benefit,” Miguel Forte, MD, PhD, CEO of Kiji Therapeutics and chair of the International Society for Cell & Gene Therapy, tells GEN. Animal studies to date suggest they are approximately 70% more effective, “but we will have to confirm that in clinical trials,” Forte says.
Kiji’s CEO, Miguel Forte, MD, PhD, is exploring inter-actions with larger companies with complementary products to help advance his company’s MSC and iPSC products toward commercialization.
Preclinical studies in NSG mice to compare Kiji’s therapeutic to WT-MSC treatment showed, at 21 days, that the CXCR4/IL-10 treated mice had gained approximately five percent of their body weight and had a GvHD score of one. The WT-MSC-treated mice, in contrast, lost approximately three percent of their body weight and had a GvHD score of four. Similarly notable effects were seen in IBD, with 80% of mice experiencing a long-term (16-day) response, suggesting the potential therapeutic may positively affect the innate immune system.
Forte says he expects manufacturing these engineered cells to be straightforward. Their first-generation manufacturing system already can produce an off-the-shelf product for clinical trials, using donor cells that are expanded and engineered. “That gives us enough cells and a reasonable cost of goods, with a value proposition that will enable us to take [some eventual] third-generation product to the market,” Forte says.
The second generation of manufacturing, expected in about 24 months, however, will use an iPSC cell line rather than donor cells, he says. This will ensure greater consistency and scalability, less cost, and, Forte says, “the ability to deliver large quantities of product at a very attractive value proposition.”
Markets and merger
Last autumn, Kiji announced a planned merger with REGiMMUNE, a Taiwanese company. That plan has since been halted and the two will continue their development independently.
That doesn’t mean other collaborations are off the table. Forte says he plans to continue establishing the data and, about midway in the clinical development process, would welcome a big pharma partner with a complementary product portfolio. Currently, he says, “We continue to explore interactions in Taiwan and with other companies.”
Since Kiji’s market is physicians (i.e., hematologists, gastroenterologists, and–for future psoriasis indications–rheumatologists and dermatologists), it would be mutually advantageous to partner with a company that already has first-line products in these indications along with an existing sales force. Such a partnership, Forte points out, would allow the larger company to not only present its own, first-line therapeutic, but to also be able to present a second-line therapeutic–Kiji’s–for patients who need an alternative.
The company is open to licensing or acquisition discussions to advance these emerging therapeutics to commercialization. The more immediate plan, however, is to develop access to the necessary technologies, team, and funding for clinical development. To do this, “We’re actively pursuing interactions with venture capitalists,” Forte says. “The subsequent challenge is to put the value that we generate in the clinic in the right position vis-à-vis the competition, clinical needs, and patient and physician needs.”
The projects that most capture Forte’s imagination, he says, are those with interesting scientific questions, development potential, and a value proposition that can return patients to normal lives. That makes IBD particularly interesting to him.
“IBD is a condition that is still very limiting for patients,” Forte points out. “These are normally young, active people who have problems that limit their social lives… work lives… private lives.”
While the IBD population shares multiple characteristics, “Recent publications have shone there is one phenotype that depends on one aggressive cell–the macrophage. Those macrophage-dependent patients can be identified by their genetic profile,” Forte says.
“What we’ve seen in preclinical data is that we’re able to control the models of IBD and, in particular, we’re able to switch the activity of those aggressive cells. I would like to confirm that, expand that, and [develop] a very strong, targeted mechanism of action and defined value proposition for those patients.”
A bridge for renewal
That combination of interesting science, development potential, and the ability to make a positive difference in patients’ lives is, in fact, what drew Forte to Kiji.
Forte came across this technology when a Parisian venture capital group asked him to conduct due diligence on a technology in Madrid. As Forte recollects, “I did my report, saying this is exciting and brings value to patients. It’s really what cell therapy is about, using the cell function optimized by gene editing.
“They said, ‘Would you like to join us and fund the company?’” He did, and Kiji Therapeutics was formed in early 2023.
The name, Kiji, was intended to be inspirational and connote a sense of renewal. It also needed to reflect the company’s Spanish and French roots. “We identified an island (uninhabited) in the Bidasoa River between France and Spain, called Pheasant Island,” he recalls. Its governance alternates between the two countries every six months.
“But, ‘pheasant’ is not a great name for a biotech, so we looked around. In Japanese, ‘kiji’ means pheasant as well as ‘phoenix.’” That chosen name, therefore, connotes not only a bridge between France and Spain but the hope of renewal.
The young company, headquartered in Paris, still collaborates with the Madrid research group. With manufacturing issues ironed out and materials ready to submit to regulators, “We aim to be in the clinic by the end of this year or early next year,” Forte says.
Kiji Therapeutics
Location: 4 Rue Thenard, Paris 05, France
Contact: [email protected]
Website: kiji-tx.com
Principal: Miguel Forte, MD, PhD, CEO
Number of Employees: 4
Focus: A pre-clinical company developing genetically engineered mesenchymal stem cell and induced pluripotent stem cel therapies for inflammatory diseases.
The post Bridging Technologies Renew Hope for Treating Inflammatory Diseases appeared first on GEN - Genetic Engineering and Biotechnology News.