Pipeline
DEVELOPMENT ENGINE ADDRESSING UNMET NEEDS
At United Therapeutics, we are at the forefront of developing novel treatments and health technologies for rare and life-threatening conditions with a focus on cardiopulmonary disease and organ transplantation. Our approach combines cutting-edge science with a patient-centric focus to create innovative therapies that make a difference.
Likewise, our revolutionary organ manufacturing programs utilize advanced technology and pioneering engineering approaches aimed at increasing the supply of transplantable organs and tissues and improving outcomes for transplant recipients.We are focused on achieving this through a variety of methods including xenotransplantation, allogeneic regenerative medicine, autologous regenerative medicine, and ex-vivo lung perfusion.
Our pipeline is dynamic and evolves regularly. Please refer to our most recent public filings for the latest updates.
Please see our Forward Looking Statements for risks and uncertainities associated with our pipeline.
TYVASO® PLATFORM
TETON 1
Idiopathic Pulmonary Fibrosis – U.S. and Canada
We are conducting two phase 3 studies, called TETON 1 and TETON 2, of nebulized treprostinil for the treatment of idiopathic pulmonary fibrosis (IPF).
About IPF. Idiopathic pulmonary fibrosis is a scarring disease of the lungs of an unknown (idiopathic) cause and is the most common of the idiopathic interstitial pneumonias. IPF is characterized by the progressive loss of the ability of the lungs to transfer oxygen into the blood, ultimately resulting in respiratory failure and death. While the precise causes of IPF remain unknown, IPF rarely presents before age 50 and can be associated with cigarette smoking and certain genetic dispositions. In addition, some evidence suggests that gastroesophageal reflux (acid reflux, or heartburn), certain viral infections, air pollution, and some exposures in the workplace may be risk factors for IPF. According to recent research, IPF is estimated to affect between 0.33 and 4.51 people per 10,000 persons worldwide. We believe there are approximately 100,000 IPF patients in the United States.
Study design. TETON 1 is being conducted in the United States and Canada and sought to enroll 576 patients; the study ultimately enrolled 598 patients. The primary endpoint for TETON 1 is the change in absolute forced vital capacity (FVC) from baseline to week 52. The secondary endpoints are time to clinical worsening, time to first acute IPF exacerbation, OS, and changes in % predicted FVC, King’s Brief Interstitial Lung Disease (K-BILD) quality of life questionnaire, and diffusing capacity of the lungs for carbon monoxide (DLCO).
The TETON 1 study enrolled its first patient in June 2021.
Study progress. In February 2025, the TETON 1 study reached full enrollment, enrolling a total of 598 patients. In February 2025, the data monitoring committee for the TETON 1 and TETON 2 studies completed a routine, unblinded safety review of data from nearly 1,100 patients enrolled in these studies, and unanimously recommended continuation of both trials without modification.
Orphan drug designation. In December 2020, the FDA granted orphan designation for treprostinil for the treatment of IPF. In March 2022, the European Medicines Agency also granted orphan designation for treprostinil for the treatment of IPF.
Study rationale.The TETON studies were prompted by data from the INCREASE study of nebulized treprostinil for the treatment of pulmonary hypertension associated with interstitial lung disease (PH-ILD), which demonstrated improvements in certain key parameters of lung function in pulmonary hypertension patients with fibrotic lung disease including improved absolute FVC and reduced exacerbations of underlying lung disease. Specifically, in the INCREASE study, treatment with nebulized Tyvaso resulted in significant improvements in percent predicted FVC at weeks 8 and 16, with subjects having an underlying etiology of IPF showing the greatest improvement (week 8: 2.5%; p=0.0380 and week 16: 3.5%; p=0.0147).
In May 2022, data from the INCREASE Open Label Extension (OLE) study were presented at the American Thoracic Society (ATS) International Conference, indicating that improvements in FVC were sustained for at least 64 weeks for PH-ILD patients with underlying IPF. For those patients who received placebo during the INCREASE study, marked improvements in FVC were observed following transition to nebulized Tyvaso during the OLE study. These data points, combined with substantial preclinical evidence of antifibrotic activity of treprostinil, suggest that nebulized treprostinil may offer a treatment option for patients with IPF.
Publications and resources.
The INCREASE study. Waxman, A., Restrepo-Jaramillo, R., Thenappan, T., Ravichandran, A., Engel, P., Bajwa, A., Allen, R., Feldman, J., Argula, R., Smith, P., Rollins, K., Deng, C., Peterson, L., Bell, H., Tapson, V., & Nathan, S. D. (2021). Inhaled treprostinil in pulmonary hypertension due to interstitial lung disease. New England Journal of Medicine, 384(4), 325–334; DOI: 10.1056/NEJMoa2008470
Plain-language summary of the INCREASE results. West N., Smoot K., Patzlaff N., Miceli M., and Waxman A. Plain language summary of the INCREASE study: inhaled treprostinil (Tyvaso) for the treatment of pulmonary hypertension due to interstitial lung disease. Future Cardiology 2023 19:5, 229-239 [link 1: https://www.futuremedicine.com/doi/10.2217/fca-2022-0108] [link 2: https://www.biomedicine.video/cardiopulmonary-vascular/inhaled-treprostinil-in-ph-ild-the-increase-study]
INCREASE post-hoc FVC changes in PH-IPF participants. Inhaled treprostinil and forced vital capacity in patients with interstitial lung disease and associated pulmonary hypertension: a post-hoc analysis of the INCREASE study. Nathan, S.D., Waxman, A., Rajagopal, S., Case, A., Johri, S., DuBrock, H., De La Zerda, D.J., Sahay, S., King, C., Melendres-Groves, L., Smith, P., Shen, E., Edwards, L.D., Nelsen, A., Tapson, V.F. Lancet Respir Med. 2021; 9(11): 1266–1274; DOI: 10.1016/S2213-2600(21)00165-X
INCREASE Open Label Extension. Long-term inhaled treprostinil for pulmonary hypertension due to interstitial lung disease: INCREASE open-label extension study. Waxman, A., Restrepo-Jaramillo, R., Thenappan, T., et al. European Respiratory Journal Jun 2023, 61 (6) 2202414; DOI: 10.1183/13993003.02414-2022
TETON design and rationale. Nathan, S.D., Behr, J., Cottin, V., et al. Study design and rationale for the TETON phase 3, randomised, controlled clinical trials of inhaled treprostinil in the treatment of idiopathic pulmonary fibrosis. BMJ Open Resp Res 2022;9:e001310. doi:10.1136/bmjresp-2022-001310
The Antifibrotic Effects of Inhaled Treprostinil. Kolb, M., Orfanos, S.E., Lambers, C. et al. The Antifibrotic Effects of Inhaled Treprostinil: An Emerging Option for ILD. Adv Ther 39, 3881–3895 (2022). DOI: 10.1007/s12325-022-02229-8
PH-ILD Japan Study. Seiichiro Sakao, Yasuhiro Kondoh, Kinoshita, H., Nishiyama, O., Ogo, T., Tanabe, N., Shun Minatsuki, Nakayama, K., Taniguchi, Y., Takahashi, K., Masahiro Takatsu, & Ogura, T. (2024). Efficacy, safety, and pharmacokinetics of inhaled treprostinil in Japanese patients with pulmonary hypertension associated with interstitial lung disease. Respiratory Investigation, 62(6), 980–986. https://doi.org/10.1016/j.resinv.2024.07.020.
The TETON 1 study on clinicaltrials.gov
The TETON OLE study on clinicaltrials.gov
TETON 2
Idiopathic Pulmonary Fibrosis – Rest of World ex-U.S. and Canada
We are conducting two phase 3 studies, called TETON 1 and TETON 2, of nebulized treprostinil for the treatment of idiopathic pulmonary fibrosis (IPF).
About IPF. Idiopathic pulmonary fibrosis is a scarring disease of the lungs of an unknown (idiopathic) cause and is the most common of the idiopathic interstitial pneumonias. IPF is characterized by the progressive loss of the ability of the lungs to transfer oxygen into the blood, ultimately resulting in respiratory failure and death. While the precise causes of IPF remain unknown, IPF rarely presents before age 50 and can be associated with cigarette smoking and certain genetic dispositions. In addition, some evidence suggests that gastroesophageal reflux (acid reflux, or heartburn), certain viral infections, air pollution, and some exposures in the workplace may be risk factors for IPF. According to recent research, IPF is estimated to affect between 0.33 and 4.51 people per 10,000 persons worldwide. We believe there are approximately 100,000 IPF patients in the United States.
Study design. TETON 2 was conducted outside the United States and Canada. The primary endpoint for TETON 2 was the change in absolute forced vital capacity (FVC) from baseline to week 52. The secondary endpoints were time to clinical worsening, time to first acute IPF exacerbation, Overall Survival, and changes in % predicted FVC, King’s Brief Interstitial Lung Disease (K-BILD) and diffusing capacity of the lungs for carbon monoxide (DLCO).
Study progress. In September 2025, we announced the TETON 2 study met its primary endpoint.
Orphan drug designation. In December 2020, the FDA granted orphan designation for treprostinil for the treatment of IPF. In March 2022, the European Medicines Agency also granted orphan designation for treprostinil for the treatment of IPF.
Publications and resources.
The TETON 2 study on clinicaltrials.gov
The TETON OLE study on clinicaltrials.gov
TETON PPF
Progressive Pulmonary Fibrosis
We are also enrolling a phase 3 study of nebulized treprostinil called TETON PPF for the treatment of progressive pulmonary fibrosis (PPF).
About PPF. PPF is a group of interstitial lung disease (ILD) conditions that exhibit progressive, self-sustaining fibrosis, and a similar disease course to IPF. PPF includes idiopathic interstitial pneumonias, autoimmune ILDs, chronic fibrosing hypersensitivity pneumonitis, and fibrotic ILDs related to environmental/occupational exposure. It is estimated that 13% to 40% of patients with these various ILDs will go on to develop PPF. Patients with PPF exhibit decreased lung function, poor quality of life, and increased mortality despite usual treatments for the underlying ILD. Estimates for median transplant free survival and overall survival are approximately 2.9 years and 3.7 years, respectively. We believe there are at least 60,000 PPF patients in the United States, but the number could be significantly greater as some estimates indicate the U.S. patient population could exceed 180,000.
Study design. TETON PPF is being conducted globally as a single pivotal study and seeks to enroll 698 patients. The primary endpoint for TETON PPF is the change in absolute forced vital capacity (FVC) from baseline to week 52. The secondary endpoints are time to clinical worsening; time to first acute PPF exacerbation; overall survival; and changes in % predicted FVC, King’s Brief Interstitial Lung Disease (K-BILD), and diffusing capacity of the lungs for carbon monoxide (DLCO).
Study progress. We enrolled the first patient in TETON PPF in October 2023.
Study rationale. Like TETON 1 and TETON 2 in idiopathic pulmonary fibrosis (IPF), the TETON PPF study was prompted by data from the INCREASE study.
The TETON studies were prompted by data from the INCREASE study of nebulized treprostinil for the treatment of pulmonary hypertension associated with interstitial lung disease (PH-ILD), which demonstrated improvements in certain key parameters of lung function in pulmonary hypertension patients with fibrotic lung disease including improved absolute FVC and reduced exacerbations of underlying lung disease. Specifically, in the INCREASE study, treatment with nebulized Tyvaso resulted in significant improvements in percent predicted FVC at weeks 8 and 16, with subjects having an underlying etiology of IPF showing the greatest improvement (week 8: 2.5%; p=0.0380 and week 16: 3.5%; p=0.0147). In May 2022, data from the INCREASE Open Label Extension (OLE) study were presented at the American Thoracic Society (ATS) International Conference, indicating that improvements in FVC were sustained for at least 64 weeks for PH-ILD patients with underlying IPF. For those patients who received placebo during the INCREASE study, marked improvements in FVC were observed following transition to nebulized Tyvaso during the OLE study. These data points, combined with substantial preclinical evidence of antifibrotic activity of treprostinil, suggest that nebulized treprostinil may offer a treatment option for patients with PPF.
Due to the similarities in the mechanism of fibrosis between IPF and PPF, we anticipate that anti-fibrotic therapies will impact disease progression similarly in patients with these conditions.
Publications and resources.
The TETON PPF study on clinicaltrials.gov
The TETON OLE study on clinicaltrials.gov
RALINEPAG PLATFORM
ADVANCE OUTCOMES
Pulmonary Arterial Hypertension
ADVANCE OUTCOMES is a phase 3, event-driven study of ralinepag in pulmonary arterial hypertension (PAH).
About PAH. PAH is a life-threatening disease that affects the blood vessels in the lungs and is characterized by increased pressure in the pulmonary arteries, which are the blood vessels leading from the heart to the lungs. The elevated pressure in the pulmonary arteries strains the right side of the heart as it pumps blood to the lungs. This eventually leads to right heart failure and, ultimately, death. PAH is characterized by structural changes in blood vessel walls, aggregation of platelets, and alteration of smooth muscle cell function. PAH affects about 500,000 individuals worldwide with around 50,000 people affected in the United States. Increases in the number of people diagnosed with the disease have been observed, but due to the rarity of the disease and the complexity of diagnosing it, only a small fraction of patients with PAH are treated.
Study design. ADVANCE OUTCOMES is a global, multi-center, placebo-controlled trial that includes patients on approved oral background PAH therapies. The study is targeting enrollment of approximately 700 to 1,000 patients. The primary endpoint is the time to first clinical worsening event. The secondary endpoints are change from Baseline through Week 28 in N-terminal prohormone of brain natriuretic peptide (NT-proBNP), six-minute walk distance (6MWD), World Health Organization (WHO)/New York Heart Association (NYHA) functional class (FC), REVEAL risk score, heart rate recovery (HRR) following completion of the six-minute walk test (6MWT), and health-related quality of life; proportion of subjects meeting NT-proBNP <300 pg/mL, 6MWD >440 meters, and WHO/NYHA FC I/II; time to all-cause mortality; time to first all-cause nonelective hospitalization; and safety and tolerability in subjects with PAH.
The ADVANCE OUTCOMES study enrolled its first patient in February 2019. We expect to close enrollment in mid-2025 and stop accruing clinical worsening events at the end of 2025.
Study progress.In June 2025, the ADVANCE OUTCOMES study reached full enrollment, enrolling a total of 728 participants. In October 2023, the data monitoring committee for the ADVANCE OUTCOMES study completed the fourth routine, unblinded safety review of data from nearly 510 patients enrolled in the study, and unanimously recommended continuation of the trial without modification.
Study rationale.Ralinepag is a next-generation, once-daily, oral, selective, and potent prostacyclin receptor agonist. A Phase 2 study of ralinepag in 61 PAH patients met its primary endpoint, showing a 29.8% reduction in median pulmonary vascular resistance (PVR) after 22 weeks of treatment with ralinepag compared with placebo.
After completing participation in the Phase 2 study, 45 patients entered an open-label extension (OLE) study to assess the safety and tolerability of ralinepag for long-term use in patients with PAH. The OLE study found that ralinepag had a manageable side effect profile, with a decrease in side effects for patients who continued taking ralinepag over time. Moreover, two years after entering the OLE study, the study showed that ralinepag significantly increased 6MWD by a mean of 36.3 meters, and over 85% of patients remained stable in their functional class. Additionally, hemodynamic measures taken either one or two years after entering the OLE study demonstrated significant improvements in both median PVR and mean pulmonary arterial pressure.
Publications and resources.
Enrollment and design. Channick, R.N., Humbert, M., et al. A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Ralinepag to Improve Treatment Outcomes in Subjects with Pulmonary Arterial Hypertension (ADVANCE OUTCOMES). Am J Respir Crit Care Med (2022);205:A3591.
Phase 2 open label extension manuscript. Barberà, J., Jansa, P., et al. Ralinepag Phase II Open-Label Extension Study in Patients with Pulmonary Arterial Hypertension. Adv Ther (2024). doi:10.1007/s12325-023-02769-7.
Phase 2 open label extension poster. Klings, E.S., Barberà, J.A., et al. Long-Term Data from Study APD811-007, an Open-Label Extension Study Evaluating Ralinepag for the Treatment of Pulmonary Arterial Hypertension. Am J Respir Crit Care Med (2022);205:A2149. doi:10.1164/ajrccm-conference.2022.205.1_MeetingAbstracts.A2149
Phase 2. Torres, F., Farber, H., Ristic, A., et al. Efficacy and safety of ralinepag, a novel oral IP agonist, in PAH patients on mono or dual background therapy: results from a phase 2 randomised, parallel group, placebo-controlled trial [published correction appears in Eur Respir J. 2024 Apr 18;63(4):1951030. doi: 10.1183/13993003.51030-2019]. Eur Respir J. 2019;54(4):1901030. Published 2019 Oct 10.
Phase 1 pharmacokinetics manuscript. Grundy, J.S., King, C.D., et al., Safety, tolerability, and pharmacokinetics of the selective prostacyclin receptor agonist ralinepag in single and multiple dosing studies of an immediate-release oral formulation in healthy volunteers. Pulmonary Circulation (2020), 10: 1-13 2045894020922814. doi:10.1177/2045894020922814
Preclinical publications.
Ralinepag discovery manuscript. Tran, T.A., Kramer, B., Shin, Y.J., et al. Discovery of 2-(((1r,4r)-4-(((4-Chlorophenyl (phenyl)carbamoyl)oxy)methyl)cyclohexyl)methoxy)acetate (Ralinepag): An Orally Active Prostacyclin Receptor Agonist for the Treatment of Pulmonary Arterial Hypertension. J Med Chem 2017; 60(3): 913-927. DOI: 10.1021/acs.jmedchem.6b00871
Ralinepag preclinical overview poster. Adams, J., Whittle, B., Shen, L., et al. Potency, Selectivity, and Comparative Platelet and Vascular Activity of Ralinepag Acting on Prostacyclin Receptors in Human Tissues. 6th World Symposium on Pulmonary Hypertension, 2018.
Ralinepag extended-release poster. Grundy, J., Blackburn, A., Tang, Y., et al. Clinical Pharmacokinetic Performance of a Ralinepag Extended-Release Tablet. PVRI Annual Congress on PVD, 2019.
The ADVANCE CAPACITY study on clinicaltrials.gov
The ADVANCE EXTENSION study on clinicaltrials.gov
XENO, ORGANS, AND ORGAN ALTERNATIVES
EVLP/CLES
Lung Transplant
Ex-vivo lung perfusion (EVLP) is a procedure that evaluates donor lungs, giving them a second chance at transplantation. EVLP allows physicians to monitor and evaluate the lungs prior to transplant in order to provide a clearer picture of lung health.
We have completed a pivotal study to determine the safety and effectiveness of the Centralized Lung Evaluation System (CLES) in enabling evaluation of potential donor lungs not otherwise used for transplant into subjects with end stage lung disease in need of lung transplantation.
About lung transplantation. For those living with chronic lung diseases such as idiopathic pulmonary fibrosis (IPF), pulmonary hypertension (PH), cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD), the only path forward is often lung transplant. Yet, the road to transplant has many obstacles, the largest being the availability of a suitable donor lung. Lungs not only must be a match, but they must also be healthy enough to be transplanted.
Study design. The CLES study was a multicenter, open-label study. The primary endpoint was 12-month survival. The secondary endpoints were primary graft dysfunction (PGD) at 0, 24 hours, 48 hours, and 72 hours; ventilator support duration; ICU and hospital lengths of stay; total preservation time; utilization rate; rate of chronic lung allograft dysfunction (CLAD); and assessment of adverse events.
Study progress. Enrollment and follow-up are complete. A Premarket Approval Application was submitted to the FDA for the CLES device in 2024.
Study rationale. EVLP provides an opportunity to evaluate organs before transplant.
This procedure has had an important impact on transplant medicine in the U.S. (and globally), expanding the donor pool by allowing surgeons to assess and successfully transplant organs that once would have gone unused. Devices developed to perform EVLP procedures in the U.S. are required to demonstrate safety and effectiveness through properly designed and executed clinical studies. The primary and key secondary endpoints in the CLES Pivotal Study were designed to provide safety and effectiveness data sufficient to support Premarket Approval of the device.
Publications and resources.
Large fraction of donated lungs are discarded. Reul, R.M., Loor, G., Garcha, P.S., Goss, J.A., Rana, A.A. Allograft discard risk index for lung transplantation. J Heart Lung Transplant. 2021 Dec;40(12):1658-1667. doi: 10.1016/j.healun.2021.08.017. Epub 2021 Sep 9. PMID: 34836606.
EVLP background. Tane, S., Noda, K., Shigemura, N. Ex Vivo Lung Perfusion: A Key Tool for Translational Science in the Lungs. Chest. 2017 Jun;151(6):1220-1228. doi: 10.1016/j.chest.2017.02.018. Epub 2017 Feb 24. PMID: 28238726.
Protective role of glycosaminoglycan component administration prior to transplant. Repair of Endothelial Glycocalyx Improves Lung Function during Human Ex-Vivo Lung Perfusion
Cold preservation and post-transplant mortality. Extended Cold Preservation Times Are Not Associated with Increased Post-Transplant Mortality After Ex Vivo Lung Perfusion (EVLP) at a Dedicated Facility Using a Centralized Lung Evaluation System (CLES) Mallea, J.M. et al. The Journal of Heart and Lung Transplantation, Volume 41, Issue 4, S42. DOI: 10.1016/j.healun.2022.01.096
Five-year outcomes post EVLP. 5 Year Outcomes Following Ex Vivo Lung Perfusion Using a Centralized Lung Evaluation System at a Dedicated Facility
Three-year outcomes post EVLP. Increasing Lung Transplant Availability with Normothermic Ex Vivo Lung Perfusion (EVLP) at a Dedicated Facility and a Centralized Lung Evaluation System (CLES): 3-Year Outcomes Mallea, J.M. et al.
The EVLP/CLES study on clinicaltrials.gov
EXPAND - UKidney™
End Stage Renal Disease
About End-Stage Renal Disease. According to the American Kidney Fund, there are approximately 808,000 patients with kidney failure in the United States and more than 557,000 patients on dialysis, approximately 93,000 of whom are on the U.S. kidney transplant waiting list. Only 21,000 deceased donor kidney transplants occurred in 2023 [footnote: American Kidney Fund 2024]. A 2021 study found that three years after starting dialysis, only 12% of patients had been placed on an Organ Procurement and Transplant Network kidney transplant waitlist while more than 40% died [footnote: US Renal Data System 2023] .
About UKidney: The UKidney is a development-stage kidney from a pig with ten genetic modifications designed to increase the probability of transplantation success by decreasing the human immune response. Six human genes were added to the pig genome to facilitate immune acceptance of the organ, while four genes were removed or “knocked out”: three that contribute to porcine organ rejection in humans and one that can cause organ growth beyond what is normal for humans.
Study Design. The study is a multicenter, open-label, safety and efficacy study and is intended to support FDA approval of a BLA. The study is designed as a combination phase 1/2/3 trial (sometimes referred to as a “phaseless” study) to evaluate safety and efficacy seamlessly without moving through separate phase 1, phase 2, and phase 3 studies that are typically associated with conventional drug approvals. Participants will receive a UKidney transplant followed by a 24-week post-transplant follow-up period, including the evaluation of all study endpoints and safety assessments. After the 24-week post-transplant follow-up period, participants who received a UKidney will continue to be followed for the rest of their lives, including for survival, UKidney function, and monitoring for zoonotic infections.
The first cohort will consist of six transplants at two centers. There will be a 12-week waiting period between the first and second transplants. After the initial cohort reaches at least 12 weeks post-transplant, safety and efficacy data will be reviewed by an independent Data Monitoring Committee to determine if the study should proceed to the next cohort. In addition, United Therapeutics intends to engage with the FDA after the first six transplants are completed. If safety and efficacy results are supportive, the sample size will be increased to a total of up to 50 participants to enable the study to support registration, with additional transplant centers expected to be added to the study.
Status.
In February 2024, we announced that the FDA has cleared our IND to initiate a clinical study. The first xenotransplant in this trial is expected to be performed around mid-year 2025.
Successful UKidney and UThymoKidney Tests in Preclinical Human Models: In 2021, surgeons at NYU and UAB tested UThymoKidneys and UKidneys from our genetically modified pigs in brain-dead organ donors maintained on artificial support, providing preclinical evidence that genetically modified pig organs could transcend the most proximate immunological barriers to xenotransplantation.
These studies, using a preclinical human decedent model, were conducted in brain-dead organ donors whose organs were determined to be ineligible for donation, with the consent of the donor’s family. Results of the UAB experiments were published in the American Journal of Transplantation in January 2022 and the Journal of Clinical Investigation in January 2024, and results of the NYU experiments were published in the New England Journal of Medicine in May 2022.
Publications and resources.
Pretransplant screening. Hisadome, Y., Eisenson, D.L., Santillan, M.R., Iwase, H., Yamada, K. Pretransplant Screening for Prevention of Hyperacute Graft Loss in Pig-to-primate Kidney Xenotransplantation. Transplantation. 2024 Aug 1;108(8):1749-1759. doi: 10.1097/TP.0000000000004958. Epub 2024 Jul 20. PMID: 39042769; PMCID: PMC11287055
Nonhuman primate preclinical studies. Eisenson, D., Hisadome, Y., Santillan, M. et al. Consistent survival in consecutive cases of life-supporting porcine kidney xenotransplantation using 10GE source pigs. Nat Commun 15, 3361 (2024). https://doi.org/10.1038/s41467-024-47679-6
Decedent xenokidney studies. Anderson, D.J., Jones-Carr, M., Perry, J., Kumar, V., Porrett, P.M., Locke, J.E. Genetically Modified Porcine Kidneys Have Sufficient Tissue Integrity for Use in Pig-to-Human Xenotransplantation. Annals of Surgery 280(3):p 374-382, September 2024. | DOI: 10.1097/SLA.0000000000006380
Comprehensive xenotransplantation review. Peterson, L., Yacoub, M. H., Ayares, D., Yamada, K., Eisenson, D., Griffith, B. P., Mohiuddin, M. M., Eyestone, W., Venter, J. C., Smolenski, R. T., & Rothblatt, M. (2024). Physiological Basis for Xenotransplantation from Genetically-Modified Pigs to Humans: A Review. Physiological Reviews, 104(3), 1409–1459. https://doi.org/10.1152/physrev.00041.2023
Xenotransplant landscape. Update on Xenogeneic Transplantation as Treatment for End Stage Organ Failure
Decedent xenokidney studies. Porrett, P.M., Orandi, B.J., Kumar, V., et al. First clinical-grade porcine kidney xenotransplant using a human decedent model. Am J Transplant. 2022; 22: 1037–1053. doi:10.1111/ajt.16930
Decedent xenokidney studies. Judd, E., Kumar, V., Porrett, P.M., Hyndman, K.A., Anderson, D.J., Jones-Carr, M.E., Shunk, A., Epstein, D.R., Fatima, H., Katsurada, A., Satou, R., Navar, L.G., Locke, J.E. Physiologic homeostasis after pig-to-human kidney xenotransplantation, Kidney International, Volume 105, Issue 5, 2024, Pages 971-979, ISSN 0085-2538, https://doi.org/10.1016/j.kint.2024.01.016
Decedent xenokidney studies. Locke, J.E., Kumar V., Anderson D., Porrett P.M. Normal Graft Function After Pig-to-Human Kidney Xenotransplant. JAMA Surg. 2023;158(10):1106–1108. doi:10.1001/jamasurg.2023.2774
Decedent xenokidney studies. Montgomery, R. A., Stern, J. M., Lonze, B. E., Tatapudi, V. S., Mangiola, M., Wu, M., Weldon, E., Lawson, N., Deterville, C., Dieter, R. A., Sullivan, B., Boulton, G., Parent, B., Piper, G., Sommer, P., Cawthon, S., Duggan, E., Ayares, D., Dandro, A., . . . Stewart, Z. A. (2022). Results of two cases of Pig-to-Human kidney xenotransplantation. New England Journal of Medicine, 386(20), 1889-1898. https://doi.org/10.1056/nejmoa2120238
Nonhuman primate preclinical studies. Burdorf, L., Laird, C.T., Harris, D.G., et al. Pig-to-baboon lung xenotransplantation: Extended survival with targeted genetic modifications and pharmacologic treatments. Am J Transplant. 2022; 22: 28–45. https://doi.org/10.1111/ajt.16809
Nonhuman primate preclinical studies. Cooper, D.K.C., Hara, H., Iwase, H., Yamamoto, T., Wang, Z.Y., Jagdale, A., Bikhet, M.H., Nguyen, H.Q., Foote, J.B., Paris, W.D., Ayares, D., Kumar, V., Anderson, D.J., Locke, J.E., Eckhoff, D.E. Pig kidney xenotransplantation: Progress toward clinical trials. Clin Transplant. 2021 Jan;35(1):e14139. doi: 10.1111/ctr.14139. Epub 2020 Nov 19. PMID: 33131148.
Growth hormone knockouts. Iwase, H., Ball, S., Adams, K., Eyestone, W., Walters, A., Cooper, D.K.C. Growth hormone receptor knockout: Relevance to xenotransplantation. Xenotransplantation. 2021; 28:e12652. https://doi.org/10.1111/xen.12652
Gene edits. Cooper, D.K.C, Hara, H., Iwase, H., Yamamoto, T., Li, Q., Ezzelarab, M., Federzoni, E., Dandro, A., Ayares, D. Justification of specific genetic modifications in pigs for clinical organ xenotransplantation. Xenotransplantation. 2019 Jul;26(4):e12516. doi: 10.1111/xen.12516. Epub 2019 Apr 15. PMID: 30989742; PMCID: PMC10154075.
The UKidney study on clinicaltrials.gov
*Registrational status pending agreement with the FDA.
miroliverELAP®
Acute Liver Failure
This is a Phase 1, open, single arm safety study of miroliver ELAP for the treatment of acute liver failure (ALF). ELAP is an external liver assist combination product consisting of a single-use MIRO-001 bioengineered liver graft and an extracorporeal blood circuit.
About ALF. ALF is a devastating condition that affects thousands of patients each year and the only effective treatment is liver transplantation. Unfortunately, given the lack of shortage of transplantable livers and the rapid onset of ALF, approximately 30% of patients die without access to a liver transplant.
Study design. This is a phase 1, open, single arm safety study of miroliverELAP for the treatment of acute liver failure (ALF). Subjects who present with ALF and no underlying chronic liver disease may be eligible for the study. Subjects will be treated with miroliverELAP continuously for 48 hours. The study will assess the safety of miroliverELAP as used to support liver function in an individual experiencing ALF. The primary endpoints are survival over the duration of ELAP treatment (48 hours) and serious adverse events over 32 days. The secondary endpoint is the proportion of subjects surviving 21-days post treatment initiation. A minimum of 5 subjects will be treated for 48 hours and followed for 32 days. Up to 15 subjects may be enrolled at up to 8 study sites.
Study progress. Recruiting.
Study rationale. ALF is a devastating condition caused by an acute traumatic assault on the liver. About 30% of adults who present with ALF will die. About 25% of adults present with ALF will receive a liver transplant, the only effective ALF treatment. Importantly, 25% of ALF patients are ineligible for a liver transplant and thus have no other option outside of palliative treatment. Further, ALF patients who receive a liver transplant need a lifetime of immunosuppression.
We believe miroliverELAP has the potential to perform functions of the native liver, supporting the native liver to allow the native liver additional time to recover. In vivo and in vitro demonstrations of miroliverELAP’s ability to clear ammonia suggest that miroliverELAP has the potential to address one of the primary causes of mortality in this subject population.
Publications and resources
Liver bioengineering. Li, K., Tharwat, M., Larson, E.L., Felgendreff, P., Hosseiniasl, S.M., Rmilah, A.A., Safwat, K., Ross, J.J., Nyberg, S.L. Re-Endothelialization of Decellularized Liver Scaffolds: A Step for Bioengineered Liver Transplantation. Front Bioeng Biotechnol. 2022 Mar 10;10:833163. doi: 10.3389/fbioe.2022.833163. PMID: 35360393; PMCID: PMC8960611
Preclinical bioengineered liver work. Anderson, B.D., Nelson, E.D., Joo, D. et al. Functional characterization of a bioengineered liver after heterotopic implantation in pigs. Commun Biol 4, 1157 (2021). DOI: 10.1038/s42003-021-02665-2
Sustained perfusion of bioengineered livers. Shaheen, M.F., Joo, D.J., Ross, J.J., Anderson, B.D., Chen, H.S., Huebert, R.C., Li, Y., Amiot, B., Young, A., Zlochiver, V., Nelson, E., Mounajjed, T., Dietz, A.B., Michalak, G., Steiner, B.G., Davidow, D.S., Paradise, C.R., van Wijnen, A.J., Shah, V.H., Liu, M., Nyberg, S.L. Sustained perfusion of revascularized bioengineered livers heterotopically transplanted into immunosuppressed pigs. Nat Biomed Eng. 2020 Apr;4(4):437-445. doi: 10.1038/s41551-019-0460-x. Epub 2019 Oct 14. Erratum in: Nat Biomed Eng. 2020 Apr;4(4):476. doi: 10.1038/s41551-019-0483-3. PMID: 31611679; PMCID: PMC7153989
Decellularization of animal organs for human use. Eliminating the organ transplant waiting list: The future with perfusion decellularized organs. Seetapun, D. et al. Surgery, Volume 161, Issue 6, 1474 – 1478. DOI: 10.1016/j.surg.2016.09.041
The miroliverELAP study on clinicaltrials.gov
PRECLINICAL XENO AND ORGAN ALTERNATIVE PLATFORM
EXPRESS - UHeart™
Xenotransplantation
About. The UHeart is a development-stage heart from a pig with ten genetic modifications designed to increase the probability of transplantation success by decreasing the human immune response. Six human genes were added to the pig genome to facilitate immune acceptance of the organ, while four genes were removed or “knocked out”: three that contribute to porcine organ rejection in humans and one that can cause organ growth beyond what is normal for humans.
Status.
Preclinical
First Successful Xenotransplants of Porcine Hearts: University of Maryland School of Medicine (UMSOM) surgeons have successfully transplanted UHearts into two living human patients. These procedures were authorized by the FDA on a single-patient, expanded access (also called “compassionate use”) basis. The FDA’s compassionate use regulations allow a physician to apply to use an unapproved product outside of a clinical trial to treat an individual patient with a serious or immediately life-threatening disease or condition when no satisfactory alternative therapy is available. The first patient, transplanted in January 2022, survived for approximately two months with the UHeart. In June 2022, data from this procedure were published in the New England Journal of Medicine. The second patient, transplanted in September 2023, survived for approximately six weeks with the UHeart. We and our collaborators continue to evaluate data from these human transplants.
Successful UHeart Tests in Preclinical Human Models: In June and July 2022, NYU surgeons tested two UHearts in brain-dead organ donors maintained on artificial support. These studies, using a preclinical human decedent model, were conducted in brain-dead organ donors whose organs were determined to be ineligible for donation, with the consent of the donor’s family. In each case, normal function was observed for our UHearts over a three-day study period, without signs of early rejection. The results were published in Nature Medicine in July 2023.
Publications and resources.
Live human heart transplantation. Griffith, B.P., Grazioli, A., Singh, A.K. et al. Transplantation of a genetically modified porcine heart into a live human. Nat Med (2025). DOI: 10.1038/s41591-024-03429-1
Decedent heart transplantation.Moazami, N., Stern, J.M., Khalil, K. et al. Pig-to-human heart xenotransplantation in two recently deceased human recipients. Nat Med 29, 1989–1997 (2023).https://doi.org/10.1038/s41591-023-02471-9
Growth hormone knockouts. The growth of xenotransplanted hearts can be reduced with growth hormone receptor knockout pig donors. Goerlich, Corbin E. et al. The Journal of Thoracic and Cardiovascular Surgery, Volume 165, Issue 2, e69 - e81. DOI: 10.1016/j.jtcvs.2021.07.051.
Immunosuppression. Extended Survival of 9- and 10-Gene-Edited Pig Heart Xenografts with Ischemia Minimization and CD154 Costimulation Blockade-Based Immunosuppression
Xenotransplant immunology. Short-Term Immuno-Molecular Landscape in 10-Gene Edit Pig-to-Human Heart Xenografts
Comprehensive xenotransplantation review. Physiological basis for xenotransplantation from genetically modified pigs to humans. Peterson, L., Yacoub, M.H., Ayares, D., Yamada, K., Eisenson, D., Griffith, B.P., Mohiuddin, M.M., Eyestone, W., Venter, J.C., Smolenski, R.T., & Rothblatt, M. Physiological Reviews 2024 104:3, 1409-1459. DOI:10.1152/physrev.00041.2023
First xenoheart transplant into a living human. Griffith, B. P., Goerlich, C. E., Singh, A. K., Rothblatt, M., Lau, C. L., Shah, A., Lorber, M., Grazioli, A., Saharia, K. K., Hong, S. N., Joseph, S. M., Ayares, D., & Mohiuddin, M. M. (2022). Genetically Modified Porcine-to-Human cardiac xenotransplantation. New England Journal of Medicine,387(1), 35–44. DOI: 10.1056/nejmoa2201422
Xenotransplant landscape. Update on Xenogeneic Transplantation as Treatment for End Stage Organ Failure
First xenoheart transplant into a living human. Graft dysfunction in compassionate use of genetically engineered pig-to-human cardiac xenotransplantation: a case report. Mohiuddin, M.M. et al. The Lancet, Volume 402, Issue 10399, 397 – 410. DOI: 10.1016/S0140-6736(23)00775-4
Nonhuman primate preclinical studies. Mohiuddin, M.M., Goerlich, C.E., Singh, A.K., Zhang, T., Tatarov, I., Lewis, B., Sentz, F., Hershfeld, A., Braileanu, G., Odonkor, P., Strauss, E., Williams, B., Burke, A., Hittman, J., Bhutta, A., Tabatabai, A., Gupta, A., Vaught, T., Sorrells, L., Kuravi, K., Dandro, A., Eyestone, W., Kaczorowski, D.J., Ayares, D., Griffith, B.P. Progressive genetic modifications of porcine cardiac xenografts extend survival to 9 months. Xenotransplantation. 2022 May;29(3):e12744. doi: 10.1111/xen.12744. Epub 2022 Mar 31. PMID: 35357044; PMCID: PMC10325874.
Nonhuman primate preclinical studies. Burdorf, L., Laird, C.T., Harris, D.G., et al. Pig-to-baboon lung xenotransplantation: Extended survival with targeted genetic modifications and pharmacologic treatments. Am J Transplant. 2022; 22: 28–45. DOI: 10.1111/ajt.16809
Xenoheart. Cleveland, D.C., Jagdale, A., Carlo, W.F., Iwase, H., Crawford, J., Walcott, G.P., Dabal, R.J., Sorabella, R.A., Rhodes, L., Timpa, J., Litovsky, S., O'Meara, C., Padilla, L.A., Foote, J., Mauchley, D., Bikhet, M., Ayares, D., Yamamoto, T., Hara, H., Cooper, D.K.C. The Genetically Engineered Heart as a Bridge to Allotransplantation in Infants Just Around the Corner? Ann Thorac Surg. 2022 Aug;114(2):536-544. doi: 10.1016/j.athoracsur.2021.05.025. Epub 2021 Jun 4. PMID: 34097894.
Growth hormone knockouts. Iwase, H., Ball, S., Adams, K., Eyestone, W., Walters, A., Cooper, D.K.C. Growth hormone receptor knockout: Relevance to xenotransplantation. Xenotransplantation. 2021; 28:e12652. DOI: 10.1111/xen.12652
Nonhuman primate preclinical studies. Goerlich, C.E., DiChiacchio, L., Zhang, T. et al. Heterotopic Porcine Cardiac Xenotransplantation in the Intra-Abdominal Position in a Non-Human Primate Model. Sci Rep 10, 10709 (2020). DOI: 10.1038/s41598-020-66430-x
Genetic edits. Cooper, D.K.C, Hara, H., Iwase, H., Yamamoto, T., Li, Q., Ezzelarab, M., Federzoni, E., Dandro, A., Ayares, D. Justification of specific genetic modifications in pigs for clinical organ xenotransplantation. Xenotransplantation. 2019 Jul;26(4):e12516. doi: 10.1111/xen.12516. Epub 2019 Apr 15. PMID: 30989742; PMCID: PMC10154075.
EXTEND - UThymoKidney™
Xenotransplantation
About. The UThymoKidney is a development-stage kidney from a pig with a single genetic modification, together with tissue from the pig’s thymus. The pig’s thymus tissue is intended to condition the recipient’s immune system to recognize the UThymoKidney as “self” and reduce the likelihood of rejection. The single gene that is inactivated in the pig is responsible for the synthesis of alpha-gal, a sugar on the surface of cells that can cause the immediate rejection of an organ when transplanted into the human body. Because tissues from pigs containing this modification do not contain detectable levels of the alpha-gal sugar, we refer to materials derived from this pig as GalSafe®. In December 2020, the GalSafe pig was approved by the FDA for use as human food or as a potential source for biomedical purposes. Meat from GalSafe pigs is currently being produced for individuals with alpha-gal syndrome, an allergy to meat caused by a bite from the lone star tick. This approval marked only the second FDA approval of a genetically modified animal as a source of food, and the first such approval for a mammal.
Status.
Preclinical
Successful UKidney and UThymoKidney Tests in Preclinical Human Models: In 2021, surgeons at NYU and UAB tested UThymoKidneys and UKidneys from our genetically modified pigs in brain-dead organ donors maintained on artificial support, providing preclinical evidence that genetically modified pig organs could transcend the most proximate immunological barriers to xenotransplantation. These studies, using a preclinical human decedent model, were conducted in brain-dead organ donors whose organs were determined to be ineligible for donation, with the consent of the donor’s family. Results of the UAB experiments were published in the American Journal of Transplantation in January 2022 and the Journal of Clinical Investigation in January 2024, and results of the NYU experiments were published in the New England Journal of Medicine in May 2022.
Publications and resources.
Immunosuppression. Jones-Carr, M. E., Fatima, H., Kumar, V., Anderson, D. J., Houp, J., Perry, J. C., Baker, G. A., McManus, L., Shunk, A. J., Porrett, P. M., & Locke, J. E. (2024). C5 inhibition with eculizumab prevents thrombotic microangiopathy in a case series of pig-to-human kidney xenotransplantation. Journal of Clinical Investigation. DOI: 10.1172/jci175996
Decedent xenokidney studies. Porrett, P.M., Orandi, B.J., Kumar, V., et al. First clinical-grade porcine kidney xenotransplant using a human decedent model. Am J Transplant. 2022; 22: 1037–1053. doi:10.1111/ajt.16930
Decedent xenokidney studies. Anderson, D.J., Jones-Carr, M., Perry, J., Kumar, V., Porrett, P.M., Locke, J.E. Genetically Modified Porcine Kidneys Have Sufficient Tissue Integrity for Use in Pig-to-Human Xenotransplantation. Annals of Surgery 280(3):p 374-382, September 2024. | DOI: 10.1097/SLA.0000000000006380
Comprehensive xenotransplantation review. Physiological basis for xenotransplantation from genetically modified pigs to humans. Peterson, L., Yacoub, M.H., Ayares, D., Yamada, K., Eisenson, D., Griffith, B.P., Mohiuddin, M.M., Eyestone, W., Venter, J.C., Smolenski, R.T., & Rothblatt, M. Physiological Reviews 2024 104:3, 1409-1459. DOI: 10.1152/physrev.00041.2023
Xenotransplant landscape. Update on Xenogeneic Transplantation as Treatment for End Stage Organ Failure
Alpha-gal gene edit. Kuravi, K.V., Sorrells, L.T., Nellis, J.R., Rahman, F., Walters, A.H., Matheny, R.G., Choudhary, S.K., Ayares, D.L., Commins, S.P., Bianchi, J.R., Turek, J.W. Allergic response to medical products in patients with alpha-gal syndrome. J Thorac Cardiovasc Surg. 2022 Dec;164(6):e411-e424. doi: 10.1016/j.jtcvs.2021.03.100. Epub 2021 Apr 9. PMID: 33933257; PMCID: PMC9673037.
Alpha-gal gene edit. Katiyar, K.S., Burrell, J.C., Laimo, F.A., Browne, K.D., Bianchi, J.R., Walters, A., Ayares, D.L., Smith, D.H., Ali, Z.S., Ledebur, H.C., Cullen, D.K. Biomanufacturing of Axon-Based Tissue Engineered Nerve Grafts Using Porcine GalSafe Neurons. Tissue Eng Part A. 2021 Oct;27(19-20):1305-1320. doi: 10.1089/ten.TEA.2020.0303. Epub 2021 Apr 9. PMID: 33514288; PMCID: PMC8610031.
Nonhuman primate preclinical studies. Cooper, D.K.C, Hara, H., Iwase, H., Yamamoto, T., Wang, Z.Y., Jagdale, A., Bikhet, M.H., Nguyen, H.Q., Foote, J.B., Paris, W.D., Ayares, D., Kumar, V., Anderson, D.J., Locke, J.E., Eckhoff, D.E. Pig kidney xenotransplantation: Progress toward clinical trials. Clin Transplant. 2021 Jan;35(1):e14139. doi: 10.1111/ctr.14139. Epub 2020 Nov 19. PMID: 33131148.
Gene edits. Cooper, D.K.C, Hara, H., Iwase, H., Yamamoto, T., Li, Q., Ezzelarab, M., Federzoni, E., Dandro, A., Ayares, D. Justification of specific genetic modifications in pigs for clinical organ xenotransplantation. Xenotransplantation. 2019 Jul;26(4):e12516. doi: 10.1111/xen.12516. Epub 2019 Apr 15. PMID: 30989742; PMCID: PMC10154075.
ULobe™
Allogeneic Regenerative Medicine
About. The ULobe is a development-stage engineered lung lobe alternative made using a porcine lung scaffold that is decellularized and then re-cellularized with allogeneic cells.
In 2023, our Regenerative Medicine Laboratory in Research Triangle Park, North Carolina produced 450 decellularized lung scaffolds, 220 re-cellularized lungs, and 1.7 trillion human cells for use in recellularization.
Status.
Preclinical
Publications and resources.
Repopulation of a lung matrix is a viable strategy for lung regeneration. Petersen, T.H., Calle, E.A., Zhao, L., Lee, E.J., Gui, L., Raredon, M.B., Gavrilov, K., Yi, T., Zhuang, Z.W., Breuer, C., Herzog, E., Niklason, L.E. Tissue-engineered lungs for in vivo implantation. Science. 2010 Jul 30;329(5991):538-41. doi: 10.1126/science.1189345. Epub 2010 Jun 24. PMID: 20576850; PMCID: PMC3640463.
Removal of the Gal epitope can potentially reduce adverse inflammatory reactions associated with chronic exposure to engineered organs containing xenogeneic components. Stahl E.C., Bonvillain R.W., Skillen, C.D., Burger, B.L., Hara, H., Lee, W., Trygg, C.B., Didier, P.J., Grasperge, B.F., Pashos, N.C., Bunnell, B.A., Bianchi, J., Ayares, D.L., Guthrie, K.I., Brown, B.N., Petersen, T.H.. Evaluation of the host immune response to decellularized lung scaffolds derived from α-Gal knockout pigs in a non-human primate model. Biomaterials. 2018 Dec;187:93-104. doi: 10.1016/j.biomaterials.2018.09.038. Epub 2018 Sep 28. PMID: 30312852.
Background on lung engineering. Calle, E.A., Petersen, T.H., Niklason, L.E. Procedure for lung engineering. J Vis Exp. 2011 Mar 8;(49):2651. doi: 10.3791/2651. PMID: 21445030; PMCID: PMC3197323.
Decellularization and recellularization of non-human primate lungs. Bonvillain, R.W., Scarritt, M.E., Pashos, N.C., Mayeux, J.P., Meshberger, C.L., Betancourt, A.M., Sullivan, D.E., Bunnell, B.A. Nonhuman primate lung decellularization and recellularization using a specialized large-organ bioreactor. J Vis Exp. 2013 Dec 15;(82):e50825. doi: 10.3791/50825. PMID: 24378384; PMCID: PMC4048361.
Decellularization and recellularization of non-human primate lungs. Bonvillain, R.W., Danchuk, S., Sullivan, D.E., Betancourt, A.M., Semon, J.A., Eagle, M.E., Mayeux, J.P., Gregory, A.N., Wang, G., Townley, I.K., Borg, Z.D., Weiss, D.J., Bunnell, B.A. A nonhuman primate model of lung regeneration: detergent-mediated decellularization and initial in vitro recellularization with mesenchymal stem cells. Tissue Eng Part A. 2012 Dec;18(23-24):2437-52. doi: 10.1089/ten.TEA.2011.0594. Epub 2012 Aug 23. PMID: 22764775; PMCID: PMC3501118.
ULung™
Autologous Regenerative Medicine
About. The ULung is a development stage engineered lung alternative composed of a 3D printed lung scaffold cellularized with either allogeneic human lung cells, or autologous cells, with the goal of reducing or eliminating the need for immunosuppression.
The lung scaffold used in the ULung is printed using 3D printers being developed in collaboration with 3D Systems, Inc.
Our Organ Manufacturing Group located in Manchester, New Hampshire, has achieved recognition for developing the world’s most complex 3D printed object. Its lung scaffold designs consist of a record 44 trillion voxels that lay out 4,000 kilometers of pulmonary capillaries and 200 million alveoli, which demonstrate gas exchange in preclinical models. Under our agreement with 3D Systems, we also have the exclusive right to develop additional human solid organs using 3D Systems’ printing technology.
Status.
Preclinical
IVIVA Kidney
Autologous Regenerative Medicine
About. IVIVA’s preclinical kidney product integrates patient-derived cells and a novel biomimetic scaffold to mimic important physiological functions of native kidney. The resulting graft is designed to be fully implantable and to replace the need for external kidney replacement therapy such as dialysis, without the need for immunosuppression.
IVIVA’s proprietary scaffold construction technology uses 3D printing and membrane interposition to build thinly separated hollow vascular networks which are layered to create a composite matrix of relevant human scale. This matrix is then populated with multiple types of cells to make functional tissue, creating a human scale solute-exchange graft that has the potential to replace kidney function. Autologous cells minimize risk of adverse side effects such as immune rejection, provides an unlimited supply of functional cells, and has no negative impact on possible future transplantation.
IVIVA is a wholly owned subsidiary of United Therapeutics.
Status.
Preclinical
miroliver®
Allogeneic Regenerative Medicine
About. It is estimated that 30 million people in the U.S. have some type of liver disease, and 5.5 million Americans have chronic liver disease or cirrhosis.
Chronic liver disease can be managed with medications and lifestyle changes if it has not progressed to end-stage liver disease (ESLD). Once it progresses to ESLD, a liver transplant is typically the best treatment option. Similar to all end-stage organ failures, a shortage of available organs is one of the largest challenges facing patients in need of a transplant.
Miromatrix
In our state-of-the-art facilities, we are utilizing clinical-sized implants and have achieved major preclinical milestones: successfully revascularizing a decellularized porcine liver graft with human vascular cells and demonstrated sustained perfusion for 15 days post-transplantation and recellularizing with hepatocytes and human vascular cells demonstrating key liver function both before and after transplantation in a large animal model.
Status.
Preclinical
Publications and resources.
Liver bioengineering. Li, K., Tharwat, M., Larson, E.L., Felgendreff, P., Hosseiniasl, S.M., Rmilah, A.A., Safwat, K., Ross, J.J., Nyberg, S.L. Re-Endothelialization of Decellularized Liver Scaffolds: A Step for Bioengineered Liver Transplantation. Front Bioeng Biotechnol. 2022 Mar 10;10:833163. doi: 10.3389/fbioe.2022.833163. PMID: 35360393; PMCID: PMC8960611
Preclinical studies. Anderson, B.D., Nelson, E.D., Joo, D. et al. Functional characterization of a bioengineered liver after heterotopic implantation in pigs. Commun Biol 4, 1157 (2021). DOI: 10.1038/s42003-021-02665-2
Preclinical studies. Shaheen, M.F., Joo, D.J., Ross, J.J., Anderson, B.D., Chen, H.S., Huebert, R.C., Li, Y., Amiot, B., Young, A., Zlochiver, V., Nelson, E., Mounajjed, T., Dietz, A.B., Michalak, G., Steiner, B.G., Davidow, D.S., Paradise, C.R., van Wijnen, A.J., Shah, V.H., Liu, M., Nyberg, S.L. Sustained perfusion of revascularized bioengineered livers heterotopically transplanted into immunosuppressed pigs. Nat Biomed Eng. 2020 Apr;4(4):437-445. doi: 10.1038/s41551-019-0460-x. Epub 2019 Oct 14. Erratum in: Nat Biomed Eng. 2020 Apr;4(4):476. doi: 10.1038/s41551-019-0483-3. PMID: 31611679; PMCID: PMC7153989
Transplant landscape. Eliminating the organ transplant waiting list: The future with perfusion decellularized organs. Seetapun, D. et al. Surgery, Volume 161, Issue 6, 1474 – 1478. DOI: 10.1016/j.surg.2016.09.041
mirokidney®
Allogeneic Regenerative Medicine
About. End-stage renal disease (ESRD), which is the final stage of chronic kidney disease and 9th leading cause of death in the United States, affects an estimated 100,000 people each year in the U.S.
These patients join the over 550,000 patients in America that either require chronic dialysis or dialysis while waiting for a kidney transplant. In 2018, there were more than 100,000 patients on the kidney transplant waitlist in the U.S. but only ~25,000 received a transplant. The only curative therapy for ESRD is a kidney transplant, yet the shortage of donor kidneys means many patients languish on the transplant waitlist for years while undergoing expensive and time-consuming dialysis treatment.
Miromatrix , our wholly owned subsidiary, is bioengineering transplantable kidneys based on our patented perfusion decellularization and recellularization technology with the goal of developing new options for patients who need a kidney transplant.
Status.
Preclinical
Publications and resources.
Preclinical studies. Uzarski, J. S., Beck, E. C., Russell, E. E., Vanderslice, E. J., Holzner, M. L., Wadhera, V., Adamson, D., Shapiro, R., Davidow, D. S., Ross, J. J., & Florman, S. S. (2023). Sustained in vivo perfusion of a re-endothelialized tissue engineered kidney graft in a human-scale animal model. Frontiers in Bioengineering and Biotechnology, 11. DOI: 10.3389/fbioe.2023.1184408
Transplant landscape. Eliminating the organ transplant waiting list: The future with perfusion decellularized organs. Seetapun, D. et al. Surgery, Volume 161, Issue 6, 1474 – 1478. DOI: 10.1016/j.surg.2016.09.041
Our pipeline is dynamic and can change regularly. Please see our latest public filings for the latest updates.