Research & development

With the help of its technology platform, Xintela is developing new treatments in the fields of stem cell therapy and targeted cancer therapy, with focus on indications with a high unmet medical need.

Technology Platform

Xintela's drug development in both stem cell therapy and cancer therapy is based on a unique marker technology platform that is based on specific cell surface markers (integrins).

Integrins are a family of cell surface proteins that regulate the function of cells in various body tissues and have long been used as target molecules in the development of therapies for, for example, inflammatory diseases and cancer. The marker technology is mainly based on the use of integrin α10β1 which was discovered by Evy Lundgren-Åkerlund's research group at Lund University. Lundgren-Åkerlund and colleagues have previously shown that integrin α10β1 is found on cartilage cells and is important for the function of cartilage cells and also on mesenchymal stem cells (MSC) that can develop into different cell types, including cartilage cells. This discovery is the basis for Xintela's selection of stem cells and the development of the patent-protected stem cell product XSTEM.

Research in Xintela's subsidiary Targinta has in recent years shown that integrin α10β1 is also found in certain aggressive cancer cells such as in triple-negative breast cancer and the brain tumor glioblastoma, which is the reason for Xintela's investment in oncology for the development of therapeutic antibodies targeting integrin α10β1.

Scientist working in lab with test tube

Pipeline

Indications
Discovery
Preclinical
Clinical
XSTEM
Osteoarthritis
Difficult-to-heal leg ulcers
ARDS
Other indications
EQSTEM
Joint disease horses

Stem cell therapy

In stem cell therapy, the stem cell marker integrin α10β1 is used to select and quality assure stem cells in the proprietary stem cell products XSTEM®, for the treatment of humans, and EQSTEM®, for the treatment of horses. Xintela has initiated clinical studies with the stem cell product XSTEM for the treatment of knee osteoarthritis and for the treatment of difficult-to-heal leg ulcers. The strategy is that further development of XSTEM for the treatment of ARDS (Acute Respiratory Distress Syndrome) takes place in collaboration with partners.

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XSTEM

Stem cell product XSTEM®

Xintela uses its proprietary stem cell marker, integrin α10β1, to select and quality assure stem cell products from donated fatty tissue from healthy individuals. XSTEM is patented both as a product and for therapeutic use in all indications. This gives Xintela the best conditions to develop safe and effective stem cell-based treatments for a variety of diseases.  

Xintela’s stem cell products are produced in the company’s own GMP-approved manufacturing facility, which significantly reduces both production costs and risks of delays.

Clinical study with XSTEM for the treatment of knee osteoarthritis  

In Xintela's clinical trial (Phase I/IIa), in patients with moderate knee osteoarthritis (Kellgren-Lawrence grade II-III), conducted in Australia. The study's Safety Review Committee has assessed all three dose levels as safe. Dosing at the third and last dose level is ongoing. The primary goal of the study is to show that XSTEM is safe, but also to obtain preliminary results showing that the product has DMOAD (Disease Modifying Osteoarthritis Drug) properties and can slow cartilage and joint breakdown as well as repair damaged articular cartilage and improve joint function. Xintela's preclinical results provide strong support for XSTEM to have a DMOAD effect.

In the clinical study, three different dose levels are evaluated in 24 patients with the option to add additional patients up to 54 patients. Each patient will be followed for 18 months with continuous safety evaluation as well as preliminary efficacy reading every six months.

Read more about osteoarthritis below.

Clinical study with XSTEM for the treatment of difficult-to-heal venous leg ulcers

Xintela's second clinical study (Phase I/IIa) is a study in patients with difficult-to-heal venous leg ulcers. The study is being conducted at four clinics in Sweden and patient recruitment is ongoing. Twelve patients with difficult-to-heal venous leg ulcers receive a treatment of XSTEM or placebo applied to the wound and are then followed weekly for ten weeks. The primary goal of the study is to show that the treatment is safe but also that XSTEM has a positive effect on wound healing.

Read more about difficult-to-heal leg ulcers below.

Happy couple riding a bike
Scientist in lab with samples

EQSTEM

Stem cell product EQSTEM® for joint disease in horses

Based on the company's unique marker technology, Xintela has also developed the stem cell product EQSTEM for the treatment of horses. Positive results from two preclinical studies in horses have shown strong support for the continued development of EQSTEM for osteoarthritis and other degenerative joint diseases in horses. Xintela plans to bring EQSTEM to market in cooperation with partners.

Cancer therapy

In cancer therapy (which is run by the subsidiary Targinta AB), therapeutic antibodies that specifically bind to the target molecule integrin α10β1, which is expressed on certain aggressive cancer cells, including cancer cells in triple-negative breast cancer and the brain tumor glioblastoma.

Microscopic image of integrin
Read more on Targinta's website
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Indications

Osteoarthritis (OA)

Osteoarthritis (OA) is a debilitating and painful joint disease characterized by cartilage and joint degradation and loss of chondrocyte function. It is the most common chronic disease of the joints, mainly in the knee, hip and hand, and the single most common cause of disability in older adults. It is estimated to affect about 25 percent of all individuals over 60 years of age and is on the rise due to an increasing ageing population. Pharmacological treatments offered today only provide symtomatic relief but do not treat the cause of the cartilage degradation.

Difficult-to-heal leg ulcers

Difficult-to-heal leg ulcers, including venous leg ulcers, representa major clinical problem, both in terms of suffering and pain for the patient, as well as to healthcare due to the huge financial burden for treatment costs. It is estimated that between 0.18 and 1 percent of the population is affected by venous leg ulcers. The prevalence increases with age and is estimated to 4 percent in individuals above 65 years. Current treatments of difficult-to-heal leg ulcers include compression therapy and surgery, but there are no efficient pharmacological treatments available.

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Publications

Camper, L., Hellman, U., and Lundgren-Åkerlund, E. Isolation, "Cloning, and Sequence Analysis of the Integrin Subunit α10, a β1-associated Collagen Binding Integrin Expressed on Chondrocytes." Journal of Biological Chemistry 273, 20383–20389 (1998).

Camper, L., Holmvall, K., Wängnerud, C., Aszódi, A., and Lundgren-Åkerlund, E.  "Distribution of the collagen-binding integrin α10β1 during mouse development."  Cell Tissue Res. 306, 107-116 (2001).

Bengtsson, T., Camper, L., Schneller, M., and Lundgren-Åkerlund, E.  "Characterization of the mouse integrin subunit α10 gene and comparison with its human homologue. Genomic structure, chromosomal localization and identification of splice variants." Matrix Biology 20, 565–76 (2001).

Bengtsson, T., Aszódi. A., Nicolae, C., Hunziker, E.B., Lundgren-Åkerlund, E., and Fässler, R.  "Loss of α10β1 integrin expression leads to moderate dysfunction of growth plate chondrocytes." Journal of Cell Science 118, 929–36 (2005).

Varas, L., Bryngelson Ohlsson, L., Honeth, G., Olsson, A., Bengtsson, T., Wiberg, C., Bockermann, R., Järnum, S., Richter, J., Pennigton, D., Johnstone, B., Lundgren-Åkerlund, E., and Kjellman, C. "α10 Integrin expression is up-regulated on fibroblast growth factor-2-treated mesenchymal stem cells with improved chondrogenic differentiation potential. " Stem Cells and Development 16, 965–978 (2007).

Lundgren-Åkerlund E., and Aszòdi A. "Integrin α10β1: a collagen receptor critical in skeletal development" Adv Exp Med Biol. 819:61-71. (2014)

Zeltz C, Lu N, Gullberg D. “Integrin α11β1: a major collagen receptor on fibroblastic cells" Adv Exp Med Biol. 819:73-83. (2014)

Munksgaard Thorén M., Chmielarska Masoumi K., Krona C., Huang X., Kundu S., Schmidt L., Forsberg-Nilsson K., Floyd Keep M., Englund E., Nelander S., Holmqvist B., and Lundgren-Åkerlund E. “Integrinα10,a Novel Therapeutic Target in Glioblastoma, Regulates Cell Migration,Proliferation, and Survival.” Cancers (Basel). 11, 587 (2019).

Uvebrant K., Reimer Rasmusson L., Talts JF., Alberton P., Aszodi A., and Lundgren-Åkerlund E. Integrinα10β1-selected Equine MSCs have Improved Chondrogenic Differentiation, Immunomodulatory and Cartilage Adhesion Capacity.”Ann Stem Cell Res. 2,001–009 (2019).

Delco ML., Goodale M., Talts JF.,Pownder SL., Koff MF., Miller AD., Nixon B., Bonassar LJ., Lundgren-Åkerlund E., and Fortier LA. Integrin α10β1-SelectedMesenchymal Stem Cells Mitigate the Progression of Osteoarthritis in an EquineTalar Impact Model.” Am J Sports Med. 48, 612-623 (2020).

Andersen, C., Uvebrant, K., Mori, Y. Aarsvold S., Jacobsen S., Berg LC., Lundgren Åkerlund, E., and Lindegaard C. ”Human integrin α10β1-selected mesenchymal stem cells home to cartilage defects in the rabbit knee and assume a chondrocyte-like phenotype.” Stem Cell Res Ther. 13, 206 (2022).

Edström D., Niroomand A., Stenlo M., Uvebrant K., Bölükbas DA., Hirdman G., Broberg E., Lim HC., Hyllén S, Lundgren-Åkerlund E., Pierre L., Olm F., Lindstedt S. "Integrin α10β1-selected mesenchymal stem cells reduced hypercoagulopathy in a porcine model of acute respiratory distress syndrome." Respir Res. 24(1):145 (2023).

Andersen C., Jacobsen S., Uvebrant K, Griffin, IV, JF., Vonk LA., Walters M., Berg LC., Lundgren-Åkerlund E., and Lindegaard C. "Integrinα10β1-Selected Mesenchymal Stem Cells ReducePain and Cartilage Degradation and Increase Immunomodulation in an EquineOsteoarthritis Model." Cartilage. doi: 10.1177/19476035231209402 (2023).

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