Tacrolimus

– All 12 patients in study (100%) achieved insulin independence, producing their own insulin and no longer requiring exogenous insulin therapy to manage their T1D – All 12 patients also achieved an HbA1c below 6.5%, with a mean most recent HbA1c of approximately 5.4%, representing an approximately 2.6% average improvement in HbA1c from baseline – No severe hypoglycemic episodes were reported post-transplant, compared with a history of recurrent severe hypoglycemic events prior to transplantation in all enrolled patients IRVINE, Calif., June 08, 2026 (GLOBE NEWSWIRE) -- Eledon Pharmaceuticals, Inc. (“Eledon”) (NASDAQ: ELDN) today announced updated results from an investigator-initiated trial evaluating tegoprubart, its investigational anti-CD40L antibody, as part of a calcineurin inhibitor-free immunosuppression regimen in patients with type 1 diabetes undergoing allogeneic islet cell transplantation at the University of Chicago Medicine Transplant Institute. The results were presented by trial investigator Piotr Witkowski, M.D., Ph.D., Director of the Pancreas and Islet Transplant Program at UChicago Medicine, at the American Diabetes Association 86th Scientific Sessions, taking place June 5-9, 2026, in New Orleans, Louisiana. All patients treated in the study (n=12) showed rapid improvement in glycemic control following islet transplantation and treatment with tegoprubart, with stable islet graft function observed across the cohort over a median and maximum post-transplant follow-up period of 8 and 22 months, respectively. All 12 patients achieved insulin independence, meaning that they no longer needed chronic, exogenous insulin therapy to manage their T1D. Also, all patients demonstrated a most recent hemoglobin A1C (“HbA1c”) below the diabetic threshold of 6.5%, with a mean most recent HbA1c of approximately 5.4% across the cohort. While all patients enrolled reported recurrent severe hypoglycemic events pre-transplant, no severe hypoglycemic episodes were reported following transplantation. Severe hypoglycemia is a serious complication of type 1 diabetes that may require emergency medical intervention and can cause loss of consciousness, seizures, injury, or death. Recurrent severe hypoglycemic episodes can significantly impact patients’ daily activities and quality of life. Higher levels of post-transplant islet cell engraftment were observed with the tegoprubart-based immunosuppression regimen than in historical patients treated with a tacrolimus-based immunosuppression regimen at UChicago Medicine. There were no rejection episodes, and no patients developed de novo donor-specific HLA antibodies. Tegoprubart-based immunosuppression was generally well tolerated, with immunosuppression-related adverse events generally successfully treated by lowering the mycophenolic acid dose, if necessary. Additionally, no evidence of nephrotoxicity, hypertension or neurotoxicity, which are commonly associated with tacrolimus-based immunosuppression regimens, was observed. These findings further support the potential of CD40L blockade to enable effective islet graft protection while avoiding the toxicities of calcineurin inhibitors such as tacrolimus. The investigator-initiated pilot study enrolled 12 adults with long-standing T1D undergoing allogeneic islet transplantation at UChicago Medicine with a median duration of diabetes of approximately 33 years and mean HbA1c of approximately 8.0% prior to transplantation. Participants received tegoprubart, as part of a calcineurin inhibitor-free immunosuppression regimen. Calcineurin inhibitors such as tacrolimus are commonly used to prevent transplant rejection but can be associated with kidney toxicity, hypertension, neurological side effects, and harm to insulin-producing islet cells, limiting their suitability for long-term use in patients with T1D receiving an islet cell transplant. “T1D patients have been waiting decades for a potential functional cure, and it is exciting to see the progress being made in that direction through the emerging promise of tegoprubart,” said David-Alexandre C. Gros, M.D., Chief Executive Officer of Eledon. “For people who have difficulty managing T1D, a regimen that may protect an islet cell graft without the long-term burden associated with calcineurin inhibitors, the current standard of care, could be transformational. We are proud to support this important research effort led by Dr. Witkowski and the team at UChicago Medicine. We also look forward to working closely with the FDA towards our goal of receiving regulatory guidance on a path to market for tegoprubart in islet cell transplantation later this year.” “Insulin independence without the burden of traditional immunosuppression has long been one of cell replacement therapy's biggest goals,” said Aaron Kowalski, Ph.D., Chief Executive Officer of Breakthrough T1D. “Results like these show that this goal is becoming increasingly achievable. Breakthrough T1D is proud to fund this important study.” This UChicago Medicine-initiated clinical trial is funded by Breakthrough T1D, with initial support from The Cure Alliance. Breakthrough T1D has also committed to fund a second study evaluating tegoprubart as part of a calcineurin inhibitor-free immunosuppression drug regimen to prevent islet transplant rejection in individuals with T1D and chronic kidney disease. 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. After the 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, islet cell transplantation, liver allograft transplantation and amyotrophic lateral sclerosis (ALS). Eledon is headquartered in Irvine, California. For more information, please visit the Company’s website at . Follow Eledon Pharmaceuticals on social media: LinkedIn ; X Forward-Looking Statements This press release contains forward-looking statements that involve substantial risks and uncertainties. Any statements about the company’s planned clinical trials, the development of product candidates, expected or future results of tegoprubart trials and its ability to prevent rejection in connection with islet cell 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 . 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 Jasper Gilmartin Group (858) 525 2047 stephen@gilmartinir.com Media Contact: Jenna Urban CG Life (212) 253 8881 jurban@cglife.com Source: Eledon Pharmaceuticals

iStock, Alexyz3d As the FDA tries to clarify its intent for former FDA Commissioner Marty Makary’s plausible mechanism framework for bespoke therapies, experts emphasize the importance of expanding its scope to encompass rare diseases that affect more than just one or a few individuals. Last month, the FDA held a workshop to discuss implementing its plausible mechanism pathway for individualized therapies, first introduced in November 2025 by Commissioner Marty Makary and Center for Biologics Evaluation and Research Director Vinay Prasad. Days before the May meeting, Prasad departed the FDA; a week later, Makary was also gone . Now, the status of all his initiatives is up in the air. “I would imagine there would have to be some sort of delay while they are seeking more permanent leadership,” Stacey Frisk, then executive director of the Rare Disease Company Coalition (RDCC), told BioSpace about the program prior to leaving her post on May 15. Saol Therapeutics is developing SL1009 for an ultrarare pediatric disease called pyruvate dehydrogenase complex deficiency (PDCD). When asked whether he is concerned that the plausible mechanism pathway might disappear along with Makary, CEO Dave Penake told BioSpace he is “constantly worried about making sure we deliver for these kids.” Penake is pragmatic about the FDA upheaval. “Organizations change, and so what we have control over is doing the best we can to support the science and kind of move the ball forward each day,” he continued. “That’s really the approach that we’re taking.” Since Makary and Prasad first published on the idea in The New England Journal of Medicine , the plausible mechanism pathway has been both celebrated and questioned. While the intentions behind it appear to be genuine, experts say that guidance from the FDA could be clearer. The workshop —held May 4 and cohosted by the Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER)—was intended to further elucidate the framework. A key point of clarification, according to Anna Kwilas, Gene Therapy CMC branch chief at the FDA, is that it is indeed a framework for achieving approval of applicable products through existing pathways, rather than a new approval pathway itself. Another important fact, Kwilas said, is that the framework is focused on genome editing and RNA-based therapies, including antisense oligonucleotides (ASOs)—though the concepts may also apply to other types of individualized therapies. But despite these key takeaways—and the issuance of draft guidance in February around the framework—experts say there is still a lack of clarity regarding which products may qualify. Maybe that’s okay, Penake said. From his perspective, the FDA should aim to define the pathway enough that people attempt to try to use it, “but you don’t want to over-define it so you exclude important technologies.” “They have clarity of intent. I think the spirit of the program is great,” he said. “The devil’s in the details.” Rare disease FDA’s Bespoke Pathway To Focus on Gene Editing and RNA-Based Treatments for Rare Diseases The framework, first introduced by FDA Commissioner Marty Makary and Center for Biologics Evaluation and Research head Vinay Prasad in November, was criticized for lacking detailed guidance. Agency leaders elucidated on the pathway for personalized medicines on Monday. February 23, 2026 · 3 min read · Nick Paul Taylor Read more Clarity needed on external controls The plausible mechanism framework was modeled on the case of KJ Muldoon , a little boy with an ultrarare and potentially fatal genetic disorder called CSP1 deficiency. Last year, at nine months old, Baby KJ received the world’s first bespoke CRISPR-based gene therapy. So far, the treatment has been “very successful,” former acting CDER director Tracy Beth Høeg said during the workshop. The framework is centered on seven pillars, according to slides presented at the workshop. A well-characterized disease abnormality A severely debilitating or life-threatening disease or condition occurring in a population too small to conduct a randomized trial Clinical evidence from such a population that demonstrates effectiveness and safety A well-characterized natural history in an untreated population Therapeutic targeting of the underlying abnormality, a proximal pathogenic pathway or a well-characterized downstream or compensatory mechanism with a clear mechanistic rationale Confirmation the target was successfully drugged, edited or both Demonstrated improvement in outcomes “In practice, because these are so specific, the mechanisms of these therapies are actually a bit stronger than just plausible,” FDA Office of Neuroscience Director Teresa Buracchio said, according to Pink Sheet . “They’re actually very plausible, or maybe even probable.” One question for the program’s implementation, however, is the use of external controls. Under Makary, the FDA issued guidance supporting the use of innovative trial designs, including externally controlled studies that use historical or real-world data (RWD), but several high profile rejections or rebuffs of rare disease applications supported by such controls have confused the industry. FDA FDA Reversals in Rare Disease Space Highlight Confusion Around External Controls While recent FDA guidance speaks to the agency’s support of innovative trial designs—including the use of external controls—the application of this flexibility appears to be inconsistent. One former regulator says the situation is more nuanced. April 6, 2026 · 6 min read · Heather McKenzie Read more “That doesn’t seem to be translating down well into the review staff,” Linda Marbán, CEO of Capricor Therapeutics, said during a BioSpace webinar earlier this year. For Frisk, this is the crux of the plausible mechanism framework. “The plausible mechanism framework really should be positioning about how evidence is generated and evaluated in settings where traditional evidence generation approaches aren’t necessarily feasible,” she said. The FDA should clarify that the feasibility of generating traditional, controlled evidence “may be significantly limited in certain contexts,” Frisk continued, adding that the agency “should fully utilize its tools to expedite development of rare disease products, especially when it comes to use of alternatives to traditional controls, such as the use of single arm studies, external controls, natural history, real world data.” It appears the FDA is taking further steps toward that end. On May 19, Motiur Rahman, a senior epidemiologist and policy advisor within CDER’s Office of Medical Policy, spoke at the Regulatory Education for Industry meeting, providing three case studies showing how drug sponsors can effectively use RWD to win approval of their products. The three case studies were Astellas’ Prograf for lung transplant and Bristol Myers Squibb’s Orencia to prevent acute graft-versus-host disease in 2021 and Novartis’ Zolgensma in 2019, Regulatory Focus reported . Broader scope, better biopharma fit Baby KJ stands as the shining example supporting the original conceit of the program. But the reality is that not many companies are developing N of 1 therapies. Rather, biotechs are often working on drugs for conditions afflicting very small patient populations. PDCD, for instance, affects fewer than 1,000 people in the U.S., Penake told BioSpace last December. Frisk, and the RDCC, say the principles that underpin the plausible mechanism framework “should be applied more broadly across rare disease where scientifically appropriate, rather than very small patient populations or N of 1 individualized therapies.” In fact, the FDA has continuously alluded to a broader application of the framework, including during the May workshop. But which therapies and indications will ultimately qualify remains unknown. “It’s easy to start with the bite size of like a baby KJ, [a] single base pair change that can have a dramatic outcome,” Penake said. PDCD is caused by more than one base pair change or genetic problem, he explained. “What we’re trying to understand is how do you broaden [the plausible mechanism pathway], and where’s the line that they draw, and how do you strengthen the mechanistic evidence and natural history evidence to support broadening the population that they would consider,” he said. “That’s not clear to us.” However it happens, industry experts agree that the program won’t be useful if it is indeed only applied to N of 1 situations. The economics of such a model just aren’t there. Rare diseases Cashing In on ‘Creative Fundamentals’ To Fund Rare Disease R&D Rare disease drug developers struggle to survive in a biopharma investment market that prioritizes large patient populations. Initiatives like the Orphan Therapeutics Accelerator are attempting to solve what CEO Craig Martin says is not a science problem, but a math problem. February 25, 2026 · 7 min read · Heather McKenzie Read more “Small patient populations mean lower peak revenue potential per indication, and that changes the whole risk-return calculus for traditional VCs,” Craig Martin, founder and CEO of the Orphan Therapeutics Accelerator (OTXL), told BioSpace in February. Another barrier lies in the manufacturing of such treatments, according to Deanna Portero, OTXL’s vice president of Partnerships and Innovation, who viewed the workshop. “The most important observation I made is that there continues to be a disconnect with the FDA regarding the resources available for the development of these individualized therapy programs, and the feasibility of the proposed standards given limited resources, especially on the genome editing applications where the FDA’s proposed approach in the guidance is to begin clinical trials with a level of CMC maturity that is at or near BLA standards,” Portero told BioSpace in an email. She said that while the FDA indicated that the framework might be commercially developed to justify the upfront investments, industry leaders at the workshop continued to emphasize that the commercial pre-viability of these programs is not there, and that “academics are not able to meet the standards outlined in the guidance.” Portero emphasized the importance of clarifying this point. “We want FDA to feel the pressure of this obvious and critical disconnect.” .responsive-container { display: flex; flex-wrap: wrap; border: 1px solid #ededed; font-family: Helvetica, Arial, Sans-Serif; padding: 20px 20px 10px 20px; } .column-left { flex: 1; max-width: 45%; padding: 20px 20px 10px 20px; } .column-right { flex: 2; padding: 20px 20px 10px 20px; } @media (max-width: 768px) { .column-left, .column-right { max-width: 100%; flex: 100%; padding: 10px 0; } } Subscribe to ClinicaSpace! 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