A Randomized, Multicenter, Phase III Trial of Tacrolimus/Methotrexate/Ruxolitinib Versus Post-Transplant Cyclophosphamide/Tacrolimus/Mycophenolate Mofetil in Non-Myeloablative/Reduced Intensity Conditioning Allogeneic Peripheral Blood Stem Cell Transplantation

The purpose of this study is to assess Tacrolimus/Methotrexate/Ruxolitinib versus Post-Transplant Cyclophosphamide/Tacrolimus/Mycophenolate Mofetil in Non-Myeloablative/Reduced Intensity Conditioning Allogeneic Peripheral Blood Stem Cell Transplantation

Start Date09 Dec 2024

Sponsor / Collaborator

Incyte Corp.

[+4]

NCT06552169 / Not yet recruitingPhase 2

The RETIRE Trial: A Randomized Phase 2 Trial of Adoptive Therapy With Treg Adoptive Cell Transfer (TRACT) To Prevent Rejection in Living Donor Kidney Transplant Recipients

The goal of this multi-national, multi-center, open-label, randomized Phase 2 trial is to determine the safety and efficacy of administering expanded regulatory T cells (TRK-001) to prevent allograft rejection in living donor renal transplant recipients.
Enrolled subjects will be randomized to one of 2 study arms:
Arm 1 subjects will receive standard of care immunosuppression
Arm 2 subjects will receive initial standard of care (SOC) immunosuppression and a single infusion of TRK-001. Three months after the transplant, Arm 2 subjects may be able to begin reducing their immunosuppression medication to a 1-drug regimen.
The primary outcome measures of trial are to evaluate several components indicating immunologic problems with the transplanted organ at 1-year post-transplant and to evaluate the ability for the study subjects given TRK-001 to wean to a 1-drug immunosuppression regimen.
All enrolled subjects will be followed for 5 years post-transplant.

Start Date01 Dec 2024

Sponsor / Collaborator

TRACT Therapeutics, Inc.

[+1]

NCT06265584 / Not yet recruitingPhase 2IIT

Phase II Clinical Trial of 2 Step ATG Combined with Tacrolimus and Mini Methotrexate for Prevention of Acute GVHD Post Reduced Intensity Allogeneic Stem Cell Transplant

In an effort to reduce graft versus host disease (GVHD) and enhance graft versus leukemia (GVL) effect post allogenic hematopoietic stem cell transplantation (AHSCT), recent research has focused on host immune cell depletion. Frame shifting anti-thymocyte globulin (ATG) backwards to earlier days before days 0 can result in deeper host and less graft T-cell depletion, leading to better immune reconstitution. Preliminary data where 80% of the ATG dose is given on days -6,-5,-4 and 20% given on day -1, showed effective prevention of severe acute GVHD, chronic GVHD and favorable early immune reconstitution. We hypothesize that our 2 step ATG dosing platform when combined with standard tacrolimus and mini methotrexate can prevent grade III-IV acute GVHD and chronic GVHD, resulting in improvement of GVHD/relapse free survival at one year post transplant.

Start Date28 Nov 2024

Sponsor / Collaborator

The University of Alabama at Birmingham

100 Clinical Results associated with Tacrolimus

100 Translational Medicine associated with Tacrolimus

100 Patents (Medical) associated with Tacrolimus

24,606

Literatures (Medical) associated with Tacrolimus

01 Jul 2025·Neural Regeneration Research

FK506 contributes to peripheral nerve regeneration by inhibiting neuroinflammatory responses and promoting neuron survival.

Article

Author: Xie, Wenyong ; Yuan, Yusong ; Han, Na ; Kou, Yuhui ; Ma, Bo ; Jin, Zongxue

JOURNAL/nrgr/04.03/01300535-202507000-00031/figure1/v/2024-09-09T124005Z/r/image-tiff FK506 (Tacrolimus) is a systemic immunosuppressant approved by the U.S. Food and Drug Administration. FK506 has been shown to promote peripheral nerve regeneration, however, its precise mechanism of action and its pathways remain unclear. In this study, we established a rat model of sciatic nerve injury and found that FK506 improved the morphology of the injured sciatic nerve, increased the numbers of motor and sensory neurons, reduced inflammatory responses, markedly improved the conduction function of the injured nerve, and promoted motor function recovery. These findings suggest that FK506 promotes peripheral nerve structure recovery and functional regeneration by reducing the intensity of inflammation after neuronal injury and increasing the number of surviving neurons.

01 Jan 2025·Neural Regeneration Research

A functional tacrolimus-releasing nerve wrap for enhancing nerve regeneration following surgical nerve repair

Article

Author: Zhang, Jennifer ; Feinberg, Konstantin ; Mirmoeini, Kaveh ; Cheung, Jenny ; Santerre, J. Paul ; So, Katelyn J.W. ; Borschel, Gregory H. ; Gordon, Tessa ; Daeschler, Simeon C. ; Manoraj, Marina

JOURNAL/nrgr/04.03/01300535-202501000-00036/figure1/v/2024-05-29T114527Z/r/image-tiff Axonal regeneration following surgical nerve repair is slow and often incomplete, resulting in poor functional recovery which sometimes contributes to lifelong disability. Currently, there are no FDA-approved therapies available to promote nerve regeneration. Tacrolimus accelerates axonal regeneration, but systemic side effects presently outweigh its potential benefits for peripheral nerve surgery. The authors describe herein a biodegradable polyurethane-based drug delivery system for the sustained local release of tacrolimus at the nerve repair site, with suitable properties for scalable production and clinical application, aiming to promote nerve regeneration and functional recovery with minimal systemic drug exposure. Tacrolimus is encapsulated into co-axially electrospun polycarbonate-urethane nanofibers to generate an implantable nerve wrap that releases therapeutic doses of bioactive tacrolimus over 31 days. Size and drug loading are adjustable for applications in small and large caliber nerves, and the wrap degrades within 120 days into biocompatible byproducts. Tacrolimus released from the nerve wrap promotes axon elongation in vitro and accelerates nerve regeneration and functional recovery in preclinical nerve repair models while off-target systemic drug exposure is reduced by 80% compared with systemic delivery. Given its surgical suitability and preclinical efficacy and safety, this system may provide a readily translatable approach to support axonal regeneration and recovery in patients undergoing nerve surgery.

01 Jan 2025·TALANTA

Au/Ag@ZIF-8 nanocomposite as solid phase extraction adsorbent and SERS substrate for tacrolimus label-free therapeutic drug monitoring in human serum

Article

Author: Cheng, Hao ; Wang, Ying ; Li, Xuesong ; Cao, Jinru ; Li, Lijun ; Huang, Wenyi ; Li, Yixing ; Zhan, Yaqin ; Feng, Jun ; Zeng, Huihui ; Gao, Si

Surface Enhanced Raman Scattering (SERS) has been extensively utilized in therapeutic drug monitoring (TDM) due to its rapid detection speed, high sensitivity and straightforward sample pretreatment. In this study, Au/AgNPs were obtained through the reduction of AgNO₃ on the surface of AuNPs. Subsequently, Au/AgNPs were embedded into the tetrahedral lattice of ZIF-8 MOFs, resulting in the formation of Au/Ag@ZIF-8 nanocomposites. The Au/Ag@ZIF-8 nanocomposites exhibit a robust electromagnetic enhancement of Au/Ag bimetallic nanoparticles and a considerable adsorption capacity of ZIF-8 MOFs. This enables the pre-enrichment of target molecules in the vicinity of the electromagnetic field of the Au/AgNPs, thereby enhancing the sensitivity of SERS detection. The SERS substrate also exhibits high stability and reproducibility, as well as molecular sieving effects, due to the fact that Au/AgNPs are embedded into the tetrahedral lattice of ZIF-8. A TDM method for tacrolimus (FK506) in human serum was developed by using Au/Ag@ZIF-8 nanocomposites as solid phase extraction (SPE) adsorbent and SERS substrates. The results showed that under the optimized conditions, tacrolimus exhibited satisfactory linearity within the concentration range of 10^-5-10^-11 mol L^-1, with a correlation coefficient (R²) of 0.9944, and the limit of detection (LOD) was as low as 6.4 pg mL^-1. The recoveries were observed to range between 92 % and 105 %, with an RSD of below 8 %. The method is highly sensitive, exhibiting a sensitivity that is 3-6 orders of magnitude higher than that of existing analytical techniques. It has the potential to be applied in a clinical setting to biological samples.

191

News (Medical) associated with Tacrolimus

30 Oct 2024

·www.globenewswire.com

Sandoz reports third-quarter and nine-month 2024 sales

Ad hoc announcement pursuant to art. 53 SIX Swiss Exchange Listing Rules MEDIA RELEASE Strong third-quarter biosimilars growth of 37% in constant currencies from existing portfolio and recent launchesGenerics growth acceleration driven by EuropeThird-quarter net sales¹ of USD 2.6 billion, up 12% in constant currencies (up 11% in USD)Nine-month net sales of USD 7.6 billion, up 9% in constant currencies (up 8% in USD)Net sales growth guidance increased to high-single digit in constant currencies (from mid- to high-single digit) and core EBITDA margin² guidance of around 20% confirmed Basel, October 30, 2024 – Sandoz (SIX:SDZ/OTCQX:SDZNY), the global leader in generic and biosimilar medicines, today announced net sales for the third quarter and nine months ended September 30, 2024. For the third quarter, net sales were USD 2.6 billion, an increase of 12% in constant currencies compared to the same quarter of the prior year. For the first nine months of 2024, net sales were USD 7.6 billion, an increase of 9% in constant currencies compared to the prior year. Richard Saynor, Chief Executive Officer of Sandoz, said: “We remain focused on execution, meeting key milestones in our biosimilars business and progressing on our journey as a standalone company. In recent months, we received approval for Pyzchiva® and Enzeevu™ in the US, launched Pyzchiva® in Europe and see continued strong uptake of Hyrimoz® in the US. “Net sales growth was achieved across generics and biosimilars, with generics accelerating in the third quarter and strong double-digit biosimilars growth in both the third quarter and first nine months. Additionally, all three regions contributed to this strong performance. We expect momentum in our business to continue, driving margin expansion through favorable product mix and leveraging our cost base. We have further advanced on our path to simplifying our business, including progression on the transformation program we launched earlier this year.” THIRD-QUARTER AND NINE-MONTH SALES Net sales for the third quarter were USD 2.6 billion, up 12% in constant currencies, compared to the third quarter of 2023. Volume contributed 13 percentage points of growth. This was partially offset by price erosion of 1 percentage point. Biosimilars were the key driver of growth in the quarter, while generics experienced solid demand. Growth accelerated in both businesses. Net sales for the first nine months of 2024 were USD 7.6 billion, up 9% in constant currencies compared to prior year. Volume contributed 11 percentage points of growth. This was partially offset by price erosion of 2 percentage points. The growth was primarily driven by biosimilars, with strong demand for both the base business and new in-market organic and acquired products in the US. Net sales by business Q3 2024Q3 2023 Change % 9M 20249M 2023 Change %USD millions unless indicated otherwise USDcc* USDcc*Generics 1 8541 794 34 5 5585 512 12Biosimilars 741 543 3637 2 0841 592 3132Net sales to third parties 2 5952 337 1112 7 6427 104 89 *constant currencies Generics overviewNet sales for the third quarter were USD 1.9 billion, up 4% in constant currencies, compared to the third quarter of 2023. Net sales for the first nine months were USD 5.6 billion, up 2% in constant currencies versus prior year. Growth in the Europe region accelerated in the third quarter, mainly driven by recent launches. The momentum continued in the International region, aided by demand for the antifungal agent Mycamine® and favorable pricing dynamics, partly offset by the divestment of the Chinese business. North America declined due to timing of new launches in the US. Biosimilars overviewNet sales for the third quarter were USD 741 million, up 37% in constant currencies, compared to the third quarter of 2023. Net sales for the first nine months were USD 2.1 billion, up 32% in constant currencies versus prior year. The strong double-digit biosimilars growth reflects the uptake of Hyrimoz® (adalimumab) in the US, the acquisition of Cimerli® (ranibizumab), the continued strong demand for our first-ever biosimilar, Omnitrope® (somatropin), and the launches of Tyruko® (natalizumab) and Pyzchiva® (ustekinumab) in Europe. Net sales by region Q3 2024Q3 2023 Change % 9M 20249M 2023 Change %USD millions unless indicated otherwise USDcc USDccEurope 1 3621 204 1312 3 9963 751 76North America 598 510 1718 1 7421 514 1515International 635 623 28 1 9041 839 49Net sales to third parties 2 5952 337 1112 7 6427 104 89 Europe overviewNet sales for the third quarter were USD 1.4 billion, up 12% in constant currencies, compared to the third quarter of 2023. Net sales for the first nine months were USD 4.0 billion, up 6% in constant currencies versus prior year. Strong growth in biosimilars continues, led by demand for Omnitrope® and the contribution from the recent launches of Tyruko® and Pyzchiva®. Generics momentum accelerated in the third quarter, driven by recent launches and the lapping of the strong prior-year comparison in the first half. North America overviewNet sales for the third quarter were USD 598 million, up 18% in constant currencies, compared to the third quarter of 2023. Net sales for the first nine months were USD 1.7 billion, up 15% in constant currencies versus prior year. Growth was driven by the ongoing uptake of Hyrimoz® in the US, the acquisition of Cimerli®, share gain of Omnitrope® in the US and the launch of Wyost®/Jubbonti® in Canada. This was partly offset by a decline in generics sales due to the timing of new launches in the US. International overviewNet sales for the third quarter were USD 635 million, up 8% in constant currencies, compared to the third quarter of 2023. Net sales for the first nine months were USD 1.9 billion, up 9% in constant currencies versus prior year. This was primarily a result of strong volume growth across both generics and biosimilars, contribution from the acquisition of Mycamine® in the prior year, favorable price dynamics and recent launches, partly offset by the divestment of the Chinese business in the second quarter. GUIDANCE 2024 On the back of strong momentum in its biosimilars business and solid generics demand, the company is increasing its full-year 2024 net sales guidance to high-single digit growth in constant currencies versus prior year (from mid- to high-single digit) and is confirming its core EBITDA margin guidance of around 20%. THIRD-QUARTER STRATEGIC MILESTONES Sandoz continued to execute on its strategy and passed additional milestones in its biosimilars portfolio. On July 1, the company announced the US FDA approval of biosimilar Pyzchiva® for all indications of the reference medicine. The company intends to launch Pyzchiva® in the US among the first wave of ustekinumab biosimilars in February 2025. On July 25, Sandoz announced the launch of biosimilar Pyzchiva® across Europe to treat chronic inflammatory diseases. Pyzchiva® was the first biosimilar to launch in Europe with all reference medicine strengths, including an initiation dose for Crohn’s disease. On August 12, Sandoz received FDA approval for Enzeevu™ to treat neovascular age-related macular degeneration. This approval further enhances the company’s leading US ophthalmology portfolio and increases access for patients. Launch timing will be dependent on several factors, including the progress and outcome of pending or potential litigation or any potential settlements. KEY LINKS Webcast – Live at 9am CET Analyst call presentationAnalyst consensus DISCLAIMER This media release contains forward-looking statements, which offer no guarantee with regard to future performance. These statements are made on the basis of management’s views and assumptions regarding future events and business performance at the time the statements are made. They are subject to risks and uncertainties including, but not confined to, future global economic conditions, exchange rates, legal provisions, market conditions, activities by competitors and other factors outside of the control of Sandoz. Should one or more of these risks or uncertainties materialize or should underlying assumptions prove incorrect, actual outcomes may vary materially from those forecasted or expected. Each forward-looking statement speaks only as of the date of the particular statement, and Sandoz undertakes no obligation to publicly update or revise any forward-looking statements, except as required by law.This media release includes non-IFRS financial measures as defined by Sandoz. An explanation of non-IFRS measures can be found in the Supplementary financial information of the Half-Year Report 2024. ABOUT SANDOZ Sandoz (SIX: SDZ; OTCQX: SDZNY) is the global leader in generic and biosimilar medicines, with a growth strategy driven by its Purpose: pioneering access for patients. More than 20,000 people of 100 nationalities work together to ensure 800 million patient treatments are provided by Sandoz, generating substantial global healthcare savings and an even larger social impact. Its leading portfolio of approximately 1,500 products addresses diseases from the common cold to cancer. Headquartered in Basel, Switzerland, Sandoz traces its heritage back to 1886. Its history of breakthroughs includes Calcium Sandoz in 1929, the world’s first oral penicillin in 1951, and the world’s first biosimilar in 2006. In 2023, Sandoz recorded net sales of USD 9.6 billion. CONTACTS Global Media Relations contacts Investor Relations contactsGlobal.MediaRelations@sandoz.comInvestor.Relations@sandoz.comSteffen Kurzawa+41 79 800 8501Laurent de Weck+41 79 795 7364Joerg E. Allgaeuer+49 171 838 4838Tamara Hackl+41 79 790 5217 SUPPORTING FINANCIAL INFORMATION Quarterly net sales 2024 Q1 2024Change % Q2 2024Change % Q3 2024Change %USD millions unless indicated otherwise USDcc USDcc USDccGenerics 1 86901 1 835-11 1 85434Biosimilars 6232121 7203537 7413637Net sales to third parties 2 49256 2 55579 2 5951112 Q1 2024Change % Q2 2024Change % Q3 2024Change %USD millions unless indicated otherwise USDcc USDcc USDcc Europe 1 32642 1 30823 1 3621312North America 52466 6202223 5981718International 642412 62759 63528Net sales to third parties 2 49256 2 55579 2 5951112 2023 Q1 2023Change % Q2 2023Change % Q3 2023Change % Q4 2023Change %USD millions unless indicated otherwise USDcc* USDcc* USDcc* USDcc* Generics 1 86826 1 85046 1 79454 1 92066Biosimilars 5161117 5331314 54374 6232926Net sales to third parties 2 38449 2 38358 2 33764 2 5431110 Q1 2023Change % Q2 2023Change % Q3 2023Change % Q4 2023Change %USD millions unless indicated otherwise USDcc* USDcc* USDcc* USDcc* Europe 1 2701016 1 2771412 1 204113 1 272104North America 496-5-3 508-4-2 510-4-3 6152020International 618-14 598-38 623312 656414Net sales to third parties 2 38449 2 38358 2 33764 2 5431110 ¹ Net sales in this document refer systematically to net sales to third parties. In the first nine months of 2023, third-party sales excluded sales to our former parent. Post spin-off, sales to our former parent are reported as third-party sales.² An explanation of non-IFRS measures can be found in the Supplementary financial information of the Half-Year Report 2024 Attachment 241030_Q3 and 9M Sales 2024_ Media Release.pdf

Drug ApprovalBiosimilarAcquisition

29 Oct 2024

·www.globenewswire.com

Eledon Pharmaceuticals Announces Positive Initial Data from Subjects with Type 1 Diabetes Treated with Tegoprubart as Part of an Immunosuppression Regimen Following Islet Transplantation in Investigator-Initiated Trial at UChicago Medicine

- First two out of three subjects treated with tegoprubart as part of immunosuppression regimen to prevent transplant rejection achieved insulin independence and remain insulin free, with glucose control in the normal range; Third subject was recently transplanted and is on trajectory for insulin independence - Islet engraftment in the first two subjects with tegoprubart estimated three to five times higher than engraftment in three comparable subjects receiving standard of care tacrolimus-based immunosuppression - Treatment with tegoprubart was generally well tolerated - Study data to be presented by UChicago Medicine’s team in oral presentation at the 5th IPITA/HSCI/Breakthrough T1D Stem Cells Summit IRVINE, Calif., Oct. 29, 2024 (GLOBE NEWSWIRE) -- Eledon Pharmaceuticals, Inc. (“Eledon”) (NASDAQ: ELDN) today announced positive data for the first three islet transplant recipients treated with an immunosuppression regimen that includes tegoprubart, the Company’s investigational anti-CD40L antibody, for prevention of islet transplant rejection in subjects with type 1 diabetes (T1D). The investigator-initiated trial, conducted by the research team at the University of Chicago Medicine’s Transplantation Institute, demonstrated potentially the first human cases of insulin independence achieved using an anti-CD40L monoclonal antibody therapy without the use of tacrolimus, the current standard of care for prevention of transplant rejection. The first two subjects achieved insulin independence and normal hemoglobin A1C (HbA1c) levels, a measure of average blood glucose, post-transplant. The third subject, who recently received an islet transplant, decreased insulin use by more than 60% three days following the procedure and continues on an insulin independence trajectory. Subjects on study received islet transplants combined with induction therapy, mycophenolate mofetil (MMF), and tegoprubart, given every third week by intravenous (IV) infusion. The first two subjects achieved insulin independence and presented stable islet graft function at approximately three months and six months post-transplant, respectively. Islet engraftment, measured by graft function standardized to the number of islets infused, was three to five times higher than three comparable subjects outside this study who received tacrolimus-based immunosuppression, suggesting treatment with tegoprubart is less toxic to transplanted islets resulting in improved graft survival and function. Treatment was generally well tolerated in all subjects with no unexpected adverse events or hypoglycemic episodes. After initial islet transplant, the first participant reduced insulin requirements by over 60% and normalized blood glucose control. The first patient then achieved insulin independence approximately two weeks after the second islet transplantation procedure. The data are being featured in an oral presentation at the International Pancreas and Islet Transplantation Association (IPITA), Harvard Stem Cell Institute (HSCI), and Breakthrough T1D (formerly JDRF) 5th Annual Summit on Stem Cell Derived Islets on Tuesday, October 29, 2024. “We are very pleased that tegoprubart played a pivotal role in yet another landmark advance in transplantation research through the work of Dr. Witkowski, Dr. Fung and their team at UChicago Medicine,” said David-Alexandre C. Gros, M.D., Chief Executive Officer of Eledon. “Following promising results in kidney allotransplant procedures as well as heart and kidney xenograft procedures, these data from subjects following islet transplantation further demonstrate tegoprubart’s potential to protect transplanted organs and cells. Dr. Witkowski’s study also further reinforces prior study results showing that tegoprubart may offer a favorable safety and efficacy profile compared to tacrolimus-based immunosuppression regimens.” “These data are another step in our quest to achieve a path for functional cures in type 1 diabetes,” said Piotr Witkowski, M.D., Ph.D., Director, Pancreas and Islet Transplant Program, UChicago Medicine and one of the study’s lead investigators. “For more than 30 years, we have been looking for options that can deliver target levels of immunosuppression without the side effects associated with standard of care, including toxicity to the kidneys, central nervous system and islet cells, and increased risk of diabetes and hypertension. These data further support tegoprubart as a novel immunosuppression option that can play a central role in advancing islets transplantation as a potentially transformational alternative for subjects with type 1 diabetes.” “Breakthrough T1D is proud to fund and support this research and is encouraged by the tegoprubart study showing that subjects who received islet transplants with a tacrolimus-free immunosuppressive regimen are making insulin again,” said Breakthrough T1D Chief Scientific Officer Sanjoy Dutta, Ph.D. “Islet replacement therapies are a key priority for Breakthrough T1D, and we’re committed to driving research that moves us toward a world where these therapies are available to the broader T1D community. Achieving this goal requires novel approaches to keep transplanted cells functional with a tolerable immunosuppression regimen. These results are an important step toward that goal, and we look forward to seeing additional data.” Efficacy and Safety Results The first participant was a 42-year-old female with a baseline weight of 88 kg/194 lbs (BMI of 30). At 90 days post-transplant, the participant’s HbA1c level improved to 6.0% (from 8.4% at baseline) and daily insulin dose decreased to 16 units per day (from 80 units per day at baseline). After 16 weeks, the participant received a second islet transplant, and approximately two weeks later achieved insulin independence, maintaining improved HbA1c levels of 5.4% afterwards. The second participant was a 30-year-old female with a baseline weight of 50 kg/110 lbs (BMI of 21). This patient stopped insulin support (from 60 units per day at baseline) four weeks after the islet transplant. Her HbA1c levels improved to 5.8% and below (from 8.5% at baseline) starting at seven weeks after the transplant. The third participant was a 37-year-old male with a baseline weight of 92 kg/203 lbs (BMI of 30) with a baseline HbA1C of 9.3%. This patient was discharged home on day three post-transplant, requiring 29 units of insulin (from 90 units per day at baseline). The treatment was generally well tolerated in all subjects with no unexpected adverse events, severe hypoglycemic episodes, or graft rejection. In January 2024, Eledon announced that it would be supplying tegoprubart for this investigator-led clinical trial with the UChicago Medicine Transplantation Institute for pancreatic islet transplantation in subjects with type 1 diabetes (NCT06305286). Tegoprubart is the cornerstone component of the chronic immunosuppressive regimen for trial participants and is being evaluated for the prevention of transplant rejection in the trial. Funding for the study includes grants from Breakthrough T1D (formerly known as JDRF) and The Cure Alliance. About Islet Transplantation for Type 1 Diabetes Pancreatic islet transplantation is a minimally invasive procedure developed to provide blood glucose control for subjects with type 1 diabetes and minimize or eliminate dependence on insulin. During the procedure, pancreatic islets containing insulin-producing beta cells are isolated from the pancreas of a deceased organ donor and infused through a small catheter into the patient’s liver. The islet cells lodge in small blood vessels in the liver and release insulin. Post-procedure, subjects remain on immunosuppression therapy to prevent transplant rejection. About Eledon Pharmaceuticals and tegoprubart Eledon Pharmaceuticals, Inc. is a clinical stage biotechnology company that is developing immune-modulating therapies for the management and treatment of life-threatening conditions. The Company’s lead investigational product is tegoprubart, an anti-CD40L antibody with high affinity for the CD40 Ligand, a well-validated biological target that has broad therapeutic potential. The central role of CD40L signaling in both adaptive and innate immune cell activation and function positions it as an attractive target for non-lymphocyte depleting, immunomodulatory therapeutic intervention. The Company is building upon a deep historical knowledge of anti-CD40 Ligand biology to conduct preclinical and clinical studies in kidney allograft transplantation, xenotransplantation, and amyotrophic lateral sclerosis (ALS). Eledon is headquartered in Irvine, California. For more information, please visit the Company’s website at www.eledon.com. Follow Eledon Pharmaceuticals on social media: LinkedIn; Twitter Forward-Looking Statements This press release contains forward-looking statements that involve substantial risks and uncertainties. Any statements about the company’s future expectations, plans and prospects, including statements about planned clinical trials, the development of product candidates, expected timing for initiation of future clinical trials, expected timing for receipt of data from clinical trials, expected or future results of tegoprubart trials and its ability to prevent rejection in connection with islet cell transplantation or kidney transplantation, as well as other statements containing the words “believes,” “anticipates,” “plans,” “expects,” “estimates,” “intends,” “predicts,” “projects,” “targets,” “looks forward,” “could,” “may,” and similar expressions, constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are inherently uncertain and are subject to numerous risks and uncertainties, including: risks relating to the safety and efficacy of our drug candidates; risks relating to clinical development timelines, including interactions with regulators and clinical sites, as well as patient enrollment; and risks relating to costs of clinical trials and the sufficiency of the company’s capital resources to fund planned clinical trials. Actual results may differ materially from those indicated by such forward-looking statements as a result of various factors. These risks and uncertainties, as well as other risks and uncertainties that could cause the company’s actual results to differ significantly from the forward-looking statements contained herein, are discussed in our quarterly 10-Q, annual 10-K, and other filings with the U.S. Securities and Exchange Commission, which can be found at www.sec.gov. Any forward-looking statements contained in this press release speak only as of the date hereof and not of any future date, and the company expressly disclaims any intent to update any forward-looking statements, whether as a result of new information, future events or otherwise. Investor Contact: Stephen JasperGilmartin Group(858) 525 2047stephen@gilmartinir.com Media Contact: Jenna UrbanBerry & Company Public Relations(212) 253 8881jurban@berrypr.com Source: Eledon Pharmaceuticals

Clinical ResultImmunotherapyClinical Study

29 Oct 2024

·endpts.com

Two type 1 diabetes patients are insulin-free after Eledon's immunosuppressant and an islet transplant

Eledon Pharmaceuticals’ experimental immunosuppressant helped two patients with type 1 diabetes go insulin-free following an islet cell transplant, the company announced Tuesday. The company’s stock $ELDN rose about 12% on Tuesday morning after Eledon announced the data and an $85 million offering . It said the investigator-initiated trial, which is being conducted by researchers at UChicago Medicine Transplant Institute, could have produced the first results showing that two patients became insulin-independent after undergoing treatment with an anti-CD40L monoclonal antibody and without taking tacrolimus, which is the current standard of care to prevent transplant rejections. Tacrolimus, a type of immunosuppressant, comes with a laundry list of toxicity issues, including kidney and beta cell toxicity, post-transplant new-onset diabetes, hypertension, brain fog and tremors, according to Eledon CEO David-Alexandre Gros. “We’re trying to get people off insulin, and yet, right when we’re giving them new islet cells, we’re giving them a drug that is going to harm,” Gros told Endpoints News . “We’re looking to develop a new generation of immunomodulator, one that will be both more effective as well as safer than the current standard of care.” Gros pointed to Vertex’s work in stem cell-derived islet cell therapy — the company announced over the summer that three of its patients had gone insulin-free using VX-880 — but patients also have to be on chronic immunosuppressive therapy. Vertex is working on VX-264, which is designed to treat patients without immunosuppressants, but Gros thinks there will be a place for Eledon’s drug, called tegoprubart, if VX-264 fails. “What we’re hoping to do is to unlock this market if tegoprubart can provide as good or better protection but without all of the side effects,” Gros said. “And so far, the data is very encouraging.” In the study, patients received islet transplants combined with induction therapy — mycophenolate mofetil plus tegoprubart — every three weeks by an IV infusion. The company said treatment with tegoprubart was “generally well-tolerated” in all subjects, with no unexpected adverse events, graft rejection or hypoglycemic episodes. A third patient decreased their insulin use by more than 60% three days after the transplant procedure. Along with achieving insulin independence at approximately three months and six months post-transplant, the first two patients also recorded normal HbA1c levels. All three patients saw improved islet engraftment — engraftment was three to five times higher than three comparable subjects who received only tacrolimus — and Eledon said this suggests that tegoprubart is “less toxic” to transplanted islets and led to improved graft survival and function. Back in 2020, Eledon bought tegoprubart through its acquisition of Anelixis, though the ALS Therapy Development Institute had discovered the drug. Eledon first ran a Phase 2 trial with the drug in ALS patients before pivoting to transplant rejection. It still has plans to develop the drug in ALS. The company is continuing the trial in islet cell transplant, which is designed for up to nine patients, and it has three ongoing trials in kidney transplantation. Editor’s note: This story has been updated with the name of the UChicago Medicine Transplant Institute.

Clinical ResultCell TherapyPhase 2AcquisitionImmunotherapy

100 Deals associated with Tacrolimus

External Link

KEGG	Wiki	ATC	Drug Bank
D08556	Tacrolimus	L04AD02 D11AH01	DB00864

R&D Status

Approved

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Vernal Keratoconjunctivitis	KR	Taejoon Pharm Co. Ltd.	11 Jul 2019
Lung Diseases, Interstitial	JP	Astellas Pharma, Inc.	14 Jun 2013
Small intestine transplantation rejection	JP	Astellas Pharma, Inc.	26 Jul 2011
Colitis, Ulcerative	JP	Astellas Pharma, Inc.	07 Jul 2009
Mucositis	JP	Senju Pharmaceutical Co., Ltd.	25 Jan 2008
Allograft Rejection	EU	Astellas Pharma Europe BV	23 Apr 2007
Allograft Rejection	IS	Astellas Pharma Europe BV	23 Apr 2007
Allograft Rejection	LI	Astellas Pharma Europe BV	23 Apr 2007
Allograft Rejection	NO	Astellas Pharma Europe BV	23 Apr 2007
Liver transplant rejection	EU	Astellas Pharma Europe BV	23 Apr 2007
Liver transplant rejection	IS	Astellas Pharma Europe BV	23 Apr 2007
Liver transplant rejection	LI	Astellas Pharma Europe BV	23 Apr 2007
Liver transplant rejection	NO	Astellas Pharma Europe BV	23 Apr 2007
Lupus Nephritis	JP	Astellas Pharma, Inc.	26 Jan 2007
Rejection of pancreas transplant	JP	Astellas Pharma, Inc.	19 Jan 2005
Lung transplant rejection	JP	Astellas Pharma, Inc.	31 Jan 2003
Cardiac transplant rejection	JP	Astellas Pharma, Inc.	20 Jun 2001
Myasthenia Gravis	JP	Astellas Pharma, Inc.	20 Sep 2000
Dermatitis, Atopic	JP	Maruho Co., Ltd.	16 Jun 1999
Bone marrow transplant rejection	JP	Astellas Pharma, Inc.	30 Apr 1999

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Kidney Failure, Chronic	Phase 3	US	Veloxis Pharmaceuticals A/S	28 Mar 2019
Renal and pancreas transplant rejection	Phase 3	US	Veloxis Pharmaceuticals A/S	27 Feb 2019
Tremor	Phase 3	US	Veloxis Pharmaceuticals A/S	01 Dec 2011
Kidney Diseases	Phase 3	AR	Astellas Pharma, Inc.	30 Sep 2009
Kidney Diseases	Phase 3	AT	Astellas Pharma, Inc.	30 Sep 2009
Kidney Diseases	Phase 3	BY	Astellas Pharma, Inc.	30 Sep 2009
Kidney Diseases	Phase 3	BE	Astellas Pharma, Inc.	30 Sep 2009
Kidney Diseases	Phase 3	BR	Astellas Pharma, Inc.	30 Sep 2009
Kidney Diseases	Phase 3	CA	Astellas Pharma, Inc.	30 Sep 2009
Kidney Diseases	Phase 3	CO	Astellas Pharma, Inc.	30 Sep 2009

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02582775 (CTgov)	Phase 2	Epidermolysis Bullosa	17	Donor mesenchymal stem cell infusions+Fludarabine+Cyclophosphamide+Thymoglobulin+Tacrolimus+mycophenolate mofetil (RDEB: HCT Plus MSC Arm B)	iakdfxrdts(oyeahvfomk) = htvpmljmia krgwcjbyax (sipmnhiyrd, zmplybsvmj - mkutolyhad) View more	-	19 Sep 2024
				Donor mesenchymal stem cell infusions+Fludarabine+Cyclophosphamide+Thymoglobulin+Tacrolimus+mycophenolate mofetil (RDEB: HCT Plus MSC Arm E)	iakdfxrdts(oyeahvfomk) = opylxtmkzv krgwcjbyax (sipmnhiyrd, webujrqqby - lmnruigqep) View more
NCT05501574 (GlobeNewswire) Manual	Phase 2	Lung transplant rejection	13	TFF TAC	razyyccymq(kfnyshszty) = No signs or symptoms suggestive of acute rejection. No use of pulse corticosteroids for treatment of rejection. No spirometry deterioration suggestive of acute rejection. No chest x-ray findings suggestive of acute rejection. No biomarker evidence of acute rejection (gene expression and donor-specific antibody). oxutfgbwmb (aqvmcogbvi ) View more	Positive	06 Aug 2024
NCT03480360 (CTgov)	Phase 3	Acute Myeloid Leukemia \| Chronic phase chronic myeloid leukemia \| Chronic Lymphocytic Leukemia ... View more	21	G-CSF+Fludarabine+cyclophosphamide+Tacrolimus+cellcept	tszojszpvo(axrdcuxrsv) = jgjxjymhrx qmkxkmklql (fjfxmqfjtb, zshhyqnjfl - yqifmjqufb) View more	-	23 Jul 2024
NCT03511560 (CTgov)	Phase 4	Renal transplant rejection	50	Tacrolimus (Tacrolimus, Immediate Release)	kfemsthcxt(azjczratkv) = yprfnszdbe hiupdqodch (cheqxihyfx, jlnhxifdfx - vzigxbwhps) View more	-	17 Jul 2024
				Tacrolimus Extended Release Oral Tablet (Envarsus XR)	kfemsthcxt(azjczratkv) = cpwskzfegb hiupdqodch (cheqxihyfx, rjwsneowfe - rsayuppaog) View more
NCT04225988 (CTgov)	Phase 4	Renal transplant rejection	20	Extended-release tacrolimus (Extended-release Tacrolimus)	xoyrxdpevk(fpoagxjlve) = aamrugbdsz lziavgccax (vzrnsrpyjc, rttaodkfpa - kmbrzxaczl) View more	-	10 Jul 2024
				Immediate-release tacrolimus (Immediate-release Tacrolimus)	xoyrxdpevk(fpoagxjlve) = ingjjbfeys lziavgccax (vzrnsrpyjc, yryjkiveoj - kkcnbsjdiy) View more
NCT03823768 (CTgov)	Phase 4	Neurotoxicity Syndromes \| Liver transplant rejection	30	Tacrolimus Immediate release (Arm 1: Control)	crtgneqtll(ylbrikbcuk) = jgvaoxnhdi yhwzrxirrc (ylxqiwwcor, yvatglgrxr - ulbvxrbgcr) View more	-	27 Jun 2024
				Envarsus (Arm 2: Intervention)	crtgneqtll(ylbrikbcuk) = rxkcepxdye yhwzrxirrc (ylxqiwwcor, zxmgoduhvw - rbtjddrulg) View more
EULAR2024	Not Applicable	Lung Diseases, Interstitial anti-MDA5 antibody	24	Tacrolimus-based triple-combination therapy	ncimxfqvab(eprgqshoyd) = kfvtvgisty umwgwrdllo (aqohfdkjar )	Positive	05 Jun 2024
				Ciclosporin-based triple-combination therapy	baxdtsjixk(thbeysmgks) = hqdvoggqex wechhgvxnc (ivdenaaeyd, -5 to 45) View more
EULAR2024	Not Applicable	Lung Diseases, Interstitial Maintenance anti-aminoacyl-tRNA synthetases \| anti-SS-A	42	Tacrolimus	ofqhmpunmx(eaygvoxskp) = 1 patient succumbed to cancer obnpmfebyj (vhbshjfygk ) View more	Positive	05 Jun 2024
EHA2024	Not Applicable	Hematopoietic stem cell transplantation	125	Tacrolimus continuous infusion	zfxhifiyoe(cfrbhikawp) = coebhpwjey vydtomafam (pymcltuxon ) View more	Positive	14 May 2024
NCT05501574 (Corporate Publications) Manual	Phase 2	Lung transplant rejection	8	Tacrolimus	ervxexgaxd(sgchusidfa) = none vcmwrstmqg (lhoqmjzwtl ) View more	Positive	15 Apr 2024

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