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Corporate Overview March 2025
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Forward-Looking Statements This presentation contains forward‐looking statements that involves substantial risks and uncertainties. Any statements about the company’s future expectations, plans and prospects, including statements about its strategy, future operations, development of its product candidates, and other statements containing the words “believes,” “anticipates,” “plans,” “expects,” “estimates,” “intends,” “predicts,” “projects,” “targets,” “could,” “may,” and similar expressions, constitute forward‐looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, although not all forward‐looking statements include such identifying words. Forward‐looking statements include, but are not limited to statements regarding: expectations regarding the timing for the commencement and completion of product development or clinical trials; the rate and degree of market acceptance and clinical utility of the company’s products; the company’s commercialization, marketing and manufacturing capabilities and strategy; the company’s intellectual property position and strategy; the company’s ability to identify additional products or product candidates with significant commercial potential; the company’s estimates regarding expenses, future revenue, capital requirements and needs for additional financing; developments relating to the company’s competitors and industry; and the impact of government laws and regulations. Actual results may differ materially from those indicated by such forward‐looking statements as a result of various important factors, including: the ability to develop commercially viable product formulations; the sufficiency of the company’s cash resources; the ability to obtain necessary regulatory and ethics approvals to commence additional clinical trials; whether data from early clinical trials will be indicative of the data that will be obtained from future clinical trials; whether the results of clinical trials will warrant submission for regulatory approval of any investigational product; whether any such submission will receive approval from the United States Food and Drug Administration or equivalent foreign regulatory agencies and, if we are able to obtain such approval for an investigational product, whether it will be successfully distributed and marketed. 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 annual report on Form 10‐K for the year ended December 31, 2024, and other filings with the SEC which can be found at www.sec.gov. Any forward‐looking statements contained in this presentation 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. 2 Photo: Gertrude “Trudy” Elion, inventor of azathioprine and recipient of Nobel Prize in Medicine in 1988.
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• Continued enrollment in the kidney transplant Phase 1b; interim data update expected mid-2025 • Enrollment in Phase 2 BESTOW trial of tegoprubart in kidney transplantation completed; top line data expected in 4Q 2025 • Continued enrollment in the investigator sponsored Phase 2 trial in islet cell transplantation for Type 1 diabetes; interim data update expected Q4 2025 • $140.2M in cash, cash equivalents and short-term investments as of December 31, 2024 • Forecasted sufficient to fund operations through the end of 2026 Eledon Company Highlights 3 • Tegoprubart has demonstrated the ability to: ‒ Engage B and T Cell targets ‒ Decrease pro-inflammatory biomarkers ‒ Protect both human-to-human and pig- to-human transplanted organs ‒ Achieve high kidney function (eGFR) levels post-transplant • 150+ subjects of safety data • Engineered to increase potency, half-life and manufacturability vs. other anti- CD40 approaches Optimized & Differentiated Lead Asset Strong Financial Profile Expected Milestones Note: As of March 21, 2025.
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Tegoprubart is a Pipeline in a Product Opportunity 4Note: As of March 21, 2025. Development plans and timelines may change, including based on U.S. and global regulatory interac tions. INDICATIONS DEVELOPMENT STAGE NOTESPRE-CLINICAL Early Human Trials/ PHASE 1 PHASE 2 PHASE 3 TRANSPLANTATION Kidney • Phase 2 BESTOW, ex-U.S. Phase 1b & Long-Term Extensions trials ongoing Islet Cell • U. Chicago investigator sponsored trial • Received U.S. FDA Orphan Drug Designation Liver XENOTRANSPLANTATION Kidney • Performed under U.S. FDA Expanded Access Protocol (EAP) Heart • Performed under U.S. FDA Expanded Access Protocol (EAP) NEUROINFLAMMATION Amyotrophic Lateral Sclerosis (ALS) • Received U.S. FDA Orphan Drug Designation • Seeking non-equity dilutive financing to advance program to Phase 3
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Mechanism Overview of CD40L Inflammatory Signaling • Interaction of CD40 with CD40L on immune cells mediates activation of the co-stimulatory immune pathway, controlling "cross talk” between the adaptive and innate immune systems • Maximal activation of inflammatory system is a 3-step process requiring co-stimulatory signaling – Step 1: Major histocompatibility complexes (MHC) and CD3/TCR engagement – Step 2: CD40 and CD40L binding resulting in cell division and clonal expansion – Step 3: Pro-inflammatory response by polarized T cells expressing inflammatory chemokines and cytokines • Blocking CD40L shifts polarization away from pro- inflammatory signaling to T cell anergy, apoptosis, and polarization to a Treg environment – Blocking CD40L thus does not generally result in lymphopenia often seen with immunosuppressive agents 5Source: Adapted from Kant, 2022. T cell B cell CD40L CD40 CD40L CD40 tegoprubart tegoprubart Antigen Presenting Cell CD40/CD40L Pathway and Tegoprubart Site of Action
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Tegoprubart: Potential Best-in-Class Anti-CD40/CD40L Antibody 6 Targeting CD40 Ligand vs. CD40 Receptor IgG1 vs. fusion protein or pegylated FABCD40L and CD40 CD40L only Targeting both anti-CD40L and anti-CD40 inhibits B cell polarization and class switching, as well as inhibits the pro-inflammatory polarization of CD4+ Helper T cells Blocking anti-CD40L also inhibits CD11 costimulatory receptors on antigen presenting cells, thus blocking the pro-inflammatory polarization of CD8 + Cytotoxic T cells Up to over 2x times longer half-life Blocking CD40L also polarizes CD4+ lymphocytes to FoxP3+ Regulatory T cells (Tregs), thus creating a potentially more tolerogenic environment Manufacturing advantages CD40L is more selectively expressed, providing the potential for additional safety and PK/PD/dosing advantages Less anti-drug antibodies Note: Potential advantages versus selected other CD40/CD40L clinical programs; not based on head- to-head studies. Differences versus any individual competitive program may vary.
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7 Note: Numbers are for the U.S. in 2018. Sources: Adapted from baptisthealth.com; USDHHS . Every Transplant Begins with Altruism & Each Donor Can Provide Multiple Organ Types Lungs Liver Pancreas Tissues Corneas Heart Kidneys Intestines 9K 70% 4K 25K 3K 68% performed each year 3-year survival rate performed each year last 5 years or more Improve lives for an average of 10+ YEARS Americans will benefit from tissue transplants 1 IN 20 Can help improve sight for 20 YEARS performed each year 5-year survival rate of 70% OR MORE performed each year Improve lives for an average of 10-15 YEARS NEARLY 3000 performed in the U.S. to date ~60% of organ transplants in U.S. are kidneys
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Immunosuppression is Necessary to Protect Transplanted Organs 8 Without immunosuppression, the host sees donor kidney as “foreign” and attacks (i.e., rejects) it Immunosuppression must be taken for life or the organ will be rejected even years after the transplant Source: U.S. NIH Research Matters, 2012.
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Kidney Transplantation is a Large but Highly Concentrated Market 9 Large patient population Limited expert centers and doctors 25,000+ 21,000+ Kidney transplants annually People living with a functioning kidney transplant255,000+ 188,000+ 97,000+ Americans on transplant waiting list 5,000 Americans per year die waiting for a kidney transplant ~11% of U.S. adults on waitlist are waiting for repeat transplants ~1,200 surgeons perform abdominal organ transplants in the U.S. ~250 transplant centers in the U.S. Sources: NIDDK; USRDS; DHHS OPTN; Milliman 2020; Statista 2021; Lam 2020; Novartis; Precision Reports 2023 .
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Kidney Transplantation Immunosuppression Market Represents a Multi-Billion Dollar Commercial Opportunity 10Sources: NIDDK; USRDS; DHHS OPTN; Milliman 2020; Statista 2021; Lam 2020; Astellas; Novartis; Precision Reports 2023 . End stage renal disease & transplant Medicare covers cost of immunosuppressive transplant drugs, regardless of patient age, if patient does not have other insurance Astellas reported tacrolimus global revenues of over $1.4B in FY2023 (Prograf, first FDA approval 1994) Graft failure of transplanted kidneys is the norm and expensive $50+ billion annual U.S. Medicare expenditure including kidney transplantation costs of $440,000+ / transplant Re-transplants deplete an already inadequate donor organ pool Patients returning to dialysis: costs $100,000+, ▼quality of life, <50% 5-year survival rate Global organ transplant immunosuppressant market size estimated $5.3+ billion $150,000+ average incremental U.S., medical costs per patient year after graft failure Average age of transplant is 50 years old but Average graft only functions 10-15 years so patients typically return to dialysis or need a repeat transplant
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Over 30-50% of Kidney Transplants Fail Within 10 Years on Current Transplant Standard of Care Immunosuppression 11 Transplant immunosuppression has high toxicity… …so Kidney Transplants typically only function 10-15 years Tacrolimus Adverse Events (6 months post transplant) Diabetes / Impaired Fasting Glucose 34% Renal Impairment 24% Tremor 22% Serious Infection 19% Hypertension 15% … and compliance issues… Up to 15 pills per day for life Nearly all patients miss doses and ~25% of patients are considered non-adherent 30% 40% 50% 60% 70% 80% 90% 100% 1 3 5 10 % Survival Year Kidney Graft Survival Living donor Deceased donor 50% Fail 30% Fail Sources: Shirali 2008; Engels et al. 2011; Cosio et al. 2002; Findlay 2016; Nankivell et al. 2004; Marcen 2009; SRTR Databas e 2016; NKF 2023; Saint-Marcoux et al. 2015; Vincenti 2007.
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Calcineurin Inhibitor (CNI) Side Effects Play a Leading Role in Kidney Graft Pathology Over Time 12Source: Nankivell 2003; Vincenti ATC 2018..
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Removing CNIs May Ameliorate the Kidney Transplantation Graft Failure Cycle 13Source: Nankivell 2003; ATC 2018; NIDDK; USRDS; DHHS OPTN; Milliman 2020; Statista 2021; Precision Reports 2023; UCSF .. Transplant $440,000+ avg. cost per U.S. patient Dialysis & Kidney Wait List • ~11% of adults on waitlist are for repeat transplants • ~15% to 20% mortality rate in 1st year of dialysis Graft Failure $150,000+ avg. incremental medical costs per patient post graft failure Inflammation & CNI Associated Kidney Damage • Nephrotoxicity • Hypertension • Diabetes Kidney Transplantation and Graft Failure Cycle
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Inhibition of CD40L Improved Survival vs. Other Approaches in Non- Human Primate (NHP) Kidney Transplantation Monotherapy Studies 14 Sources: Perrin, 2022; Song, 2014; Song, 2016; Duan, 2017. Note: In aggregated data from published studies, NHPs receiving anti -CD40L (e.g., 5c8, AI794, IDEC-131) immunomodulation monotherapy post kidney transplantation had longer average survival than those receiving anti-CD40 monotherapy (e.g., 4D11, cH5D12, Chi220, ASKP1240), tacrolimus monotherapy or untreated controls. Meta-analysis not based on head-to-head studies. Differences between any individual programs may vary. Tac = tacrolimus. NHP Survival Post Kidney Transplant Anti-CD40 Anti-CD40L Untreated Tac Belatacept
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NHP Renal Xenotransplantation Experience has Demonstrated Advantage of Blocking CD40L vs. Tacrolimus or CD40 15Source: Adams et al., “Anti-CD154 (aka CD40L) Costimulation Blockade is Superior to Tacrolimus in Prolonging Survival in Pig-to-Nonhuman Primate Renal Xenotransplantation,” A TC 2019. 100 75 50 25 0 0 50 100 150 200 250 300 350 400 p = 0.0031 Post-Transplant Days Percent Survival Anti-CD40 Anti-CD40LTac NHP Survival Post Xeno Kidney Transplant
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Phase 1b and Phase 2 Kidney Transplantation Studies are Enrolling in Parallel 16Note: ATG = Antithymocyte globulin. Development plans may change, including based on U.S. and global regulatory interactions. 52-week, open label, single arm study Phase 2 “BESTOW” ~120 participants (60/arm) undergoing kidney transplantation U.S. and other countries ATG induction therapy plus CNI-free maintenance therapy with tegoprubart (as a replacement for tacrolimus) as part of a maintenance immunosuppressive regimen including mycophenolate and a corticosteroid taper ATG induction therapy plus CNI-free maintenance therapy with tegoprubart or tacrolimus as part of a maintenance immunosuppressive regimen including mycophenolate and a corticosteroid taper 52-week, head-to-head, superiority study Primary endpoints: • Safety & tolerability Secondary endpoints: • Graft function (eGFR) • Participant and graft survival • Biopsy proven acute rejection (BPAR) • Immune cell infiltrate of graft biopsy • Biomarker measures of kidney injury and rejection risk Primary endpoints: • Graft function (eGFR) • Safety & tolerability Secondary endpoints: • Participant and graft survival • Biopsy proven acute rejection (BPAR) • Immune cell infiltrate of graft biopsy • Rate of new onset diabetes mellitus (NODAT) • Biomarker measures of kidney injury and rejection risk Phase 1b Up to 24 participants undergoing kidney transplantation Canada, UK and Australia
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eGFRs Over Time Post Transplant: Mean ~53 mL/min/1.73m2 After 12 Months Using CNIs 17 50 40 20 10 30 40 20 0 0 16 32 48 Days eGFR Donor type Deceased Living Treatment type CNI CNI-free 0 2 4 6 Years eGFR Note: n = 4,868 patients. eGFR estimated using MDRD 4- variable GFR Equation. Source: Kosinski et al. Clin Transl Sci. 2023 Nov; 00:1–11.
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Kidney Allograft Function is an Early Predictor of Future Graft Failure 18 eGFR at 12 months is associated with 10-year death-censored graft failure (n = 13,661 patients) Source: Kasiske et al. “Relationship Between Kidney Function and Long Term Graft Survival After Kidney Transplant.” Am J Kidney Dis. 2011. • Median eGFR of 50 mL/min/1.73m2 at 12 months (95th percentile of 83 mL at 12 months) • Graft function measured using eGFR at 12 months post transplant is associated independently with subsequent graft failure • Of multiple covariates,12-month eGFR is the strongest predictor of graft failure
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Phase 1b Kidney Transplantation Aggregate Mean eGFR CD40L Target Engagement Note: ATN = Acute Tubular Necrosis. Estimated glomerular filtration rate (eGFR) as of March 2024, calculated using the chroni c kidney disease epidemiology collaboration (CKD-EPI) creatinine equation. N is the number of participants at that time contributing data to mean eGFR calculation. Graphs use end of treatment last value. Source: Company data, ATC 2024. All Subjects Excluding Subject with Surgical Complication (ATN) on Day 0 19
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Phase 1b Kidney Transplantation: Demographics and Disposition 20 Age/ Gender Ethnicity Donor Underlying Disease Donor Age HLA Mismatch 60/F White Living Polycystic Kidney Disease 40 5 77/F White Deceased Diabetes 42 5 62/M White Living Cystic Disease 55 4 68/M White Living Diabetes 57 4 23/F Asian Living Glomerulonephritis 49 2 44/M White Deceased Polycystic Kidney Disease 42 4 65/M White Living Diabetes 64 2 57/F White Living Diabetes 45 6 35/M Other Living Glomerulonephritis 59 5 56/F White Living Cystic Disease 54 4 59/M White Living Diabetes 63 6 38/M Asian Deceased FSGS 32 5 68/M Other Deceased Diabetes 38 5 Note: Enrollment cut off for Demographics and Disposition is April 2024. Source: Company data, ATC 2024. Kosinski (CPI) et al. Clin Transl Sci. 2023 Nov; 00:1–11. • Median recipient age: 59 y.o. (vs. CPI median of 51 y.o.) • Median donor age: 49 y.o. (vs. CPI median of 44. y.o.) • Mean HLA mismatch: 4.4 / 6
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Phase 1b Kidney Transplantation: Treatment Emergent Adverse Events* 21 System Organ Preferred Term N (%) Gastrointestinal Diarrhea 5 (38%) Constipation 5 (38%) Nausea 4 (31%) Vomiting 3 (23%) Infections Polyomavirus (BK) viremia 5 (38%) Cytomegalovirus viremia 2 (15%) Upper respiratory tract infection 2 (15%) Urinary tract infection 2 (15%) Procedural Complication Transplant surgery complications 3 (23%) Procedural pain 3 (23%) Blood and Lymphatic System Leukopenia 4 (31%) Neutropenia 4 (31%) Cardiac Tachycardia 4 (31%) General Peripheral edema 2 (15%) Pyrexia 2 (15%) Metabolism Hypophosphatemia 3 (23%) Hypoglycemia 2 (15%) Musculoskeletal and Connective Tissue Pain 4 (31%) Skin and Subcutaneous tissue Alopecia 2 (15%) Vascular Hypertension 2 (15%) Hypotension 3 (23%) *Occurring in 2 or more study subjects as of data cut off. Of all the reported TEAEs, 7 events experienced by 3 subjects are reported as serious. These SAEs include neutropenia, acute kidney injury, T-cell rejection, Polyomavirus viremia, anterior abdominal wall collection, and hyperkalemia • No cases of hyperglycemia, new onset diabetes or tremor • 1 participant discontinued study on day 217 due to alopecia and fatigue, 1 participant discontinued study on day 54 due to Polyomavirus viremia, and 1 participant discontinued study on day 176 due to rejection (Banff score 2B) • 1 participant experienced a surgical procedure related kidney damage (Acute Tubular Necrosis) on day 0, prior to tegoprubart administration, which impacted their kidney function. The subject remains in the study • BK infections were controlled by temporarily decreasing immunosuppression, and CMV infections were controlled by antivirals Source: Company data, ATC 2024.
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Tegoprubart may unlock the islet cell transplant market by potentially: 1. Improving islet cell graft survival regardless of cell source (e.g., manufactured) and/or the use of a pouch 2. Reducing side effects associated with standard of care regimens including islet cell death Islet Cell Transplant Opportunity Source: Sherr et al. Severe Hypoglycemia & Impaired Awareness. Diabetes Care, 2024. Virdi et al. Prevalence, Cost, & Burden of DKA. DT&T, 2023; CDC 2024; Shapiro et al. Clinical pancreatic islet transplantation. Nature Reviews. Endocrinology. 2017;13(5):268–277. ~2 million Americans live with Type 1 diabetes (T1D) ~33% of people with T1D report Impaired Awareness of Hypoglycemia regardless of CGM or AID usage ~12% of people with T1D experience recurrent severe hypoglycemic events annually, putting them at higher risk for adverse outcomes ~5% to 8% of adults with T1D experience Diabetic Ketoacidosis (DKA) annually, often as a result of poor glycemic control Currently, islet cell transplantation is underutilized in part due to immunosuppressive regimens with CNIs that may (i) be toxic to transplanted insulin producing islet cells resulting in the need for multiple transplants and (ii) cause significant side effects 22
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Source: Quintana et al. OBM Transplantation. 2018 Islet Cell Transplant Procedure 23
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Tegoprubart Prolonged Graft Survival vs. Tacrolimus Containing Regimen (CIS) in a Non-Human Primate Islet Cell Transplant Model… 24Source: Kenyon, ATC 2021. Mean Survival (Days) Rejection Free Survival Overall Islet Graft Survival 0 50 100 150 200 250 300 350 400 Tacrolimus (n=2) Tacrolimus (n=2) Tegoprubart (n=6) Tegoprubart (n=6)
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… And Tegoprubart was Associated With Better Metabolic Control as Well as Healthier Animals Overall as Demonstrated by Body Weight 25 Tegoprubart vs. Tacrolimus Regimens in NHP Islet Cell Transplantation Model Source: Kenyon, ATC 2021. CIS-Based AT-1501-Based -0.25 -0.20 -0.15 -0.10 -0.05 0.00 0.05 0.10 0.15 0.20 Body Weight % ∆ Slope ✱ p = 0.016 TegoprubartTac TegoTacTegoTac TegoTac TegoTac
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Phase 1/2 Study Assessing the Use of Tegoprubart to Prevent Islet Cell Transplant Rejection in Participants with Type 1 Diabetes • 52-week, open label, single dose level study • Initial group of up to 3 participants with Type 1 Diabetes (T1D) at the University of Chicago – Trial designed for up to 9 participants • Islet cell transplant combined with induction therapy plus tegoprubart and mycophenolate mofetil (MMF) every third week by IV infusion • Financing principally from Breakthrough T1D (a.k.a. JDRF) and The Cure Alliance • Safety & tolerability • Graft function – e.g., HbA1C, C-peptide • Number of hypoglycemic events • Insulin independence • Need for repeat islet cell transplant(s) 26Note: Development plans may change, including based on U.S. and global regulatory interactions. PLANNED DATA GENERATIONDESIGN
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8.4 7.8 7.2 7.1 6.9 6.3 6.1 6 5.9 5.4 PRETX 1W 2W 3W 4W 7W D75 3M 4M 2W HbA1c Subject 1: Transplant Details, Insulin Use & HbA1c 27 2nd Tx Note: IEQ = Islet Equivalents, at time of transplant, defined per standard as each equaling a single spherical islet of 150 μm in diameter. Source: Witkowski, IPITA 2024. 42 years old female Weight 88kg (BMI 30) • Transplant #1 (April 2024) Islet IEQ= 363,000 Islet IEQ/kg= 4,092 • Transplant #2 (Aug. 2024) Islet IEQ= 505,000 Islet IEQ/kg= 5,500 Daily insulin use: 80u 30u 16u Insulin free 1st Tx
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Subject 1: Mixed Meal Tolerance Test 28Source: Witkowski, IPITA 2024. 0 100 200 300 400 500 0 15 30 60 90 120 180 240 Glucose (mg/dl) 0.0 1.0 2.0 3.0 4.0 0 15 30 60 90 120 180 240 C peptide (ng/ml) Minutes Minutes
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Subject 2: Transplant Details, Insulin Use & HbA1c 29 Insulin free 30 years old female Weight 50kg (BMI 21) • Transplant (July 2024) Islet IEQ= 326,000 Islet IEQ/kg= 6,775 Daily insulin use: 60u 17u 15u 8.5 8.2 7.6 7.3 6.6 5.8 PRETX 1W 2W 3W 4W 7W HbA1c Note: IEQ = Islet Equivalents, at time of transplant, defined per standard as each equaling a single spherical islet of 150 μm in diameter. Source: Witkowski, IPITA 2024.
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Subject 2: Mixed Meal Tolerance Test 30Source: Witkowski, IPITA 2024. 0 100 200 300 400 500 0 15 30 60 90 120180240 Glucose (mg/dl) 0 1 2 3 4 0 15 30 60 90 120 180 240 C peptide (ng/ml) Minutes Minutes
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Subject 3: Transplant Details 31Source: Witkowski, IPITA 2024. Day 3: Blood glucose control 37 years old male Weight 92kg (BMI 30) Baseline HbA1C 9.3% • Transplant (October 2024) Islet IEQ= 376,000 Islet IEQ/kg= 4,086 • Insulin use per day Baseline: 90u Day 3 discharge: 29u
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Day 75 Graft Function in First 2 Islet Transplant Subjects 32 Mixed Meal Tolerance Test (AUC C-peptide) Tacrolimus Sub#1 Tegoprubart Sub#2 Mixed Meal Tolerance Test (AUC C-peptide / AUC Glucose / IEQ) Tacrolimus Sub#1 Tegoprubart Sub#2 Note: IEQ = Islet Equivalents, at time of transplant, defined per standard as each equaling a single spherical islet of 150 μm in diameter. Source: Witkowski, IPITA 2024. (pmol/ml)/(mg/dl)*10^9 IEQ (pmol/ml)*min
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Islet Cell Transplant Safety Summary 33 • First 2 subjects achieved blood glucose control in normal range without insulin support • No severe hypoglycemic episodes • No infections • No evidence of nephrotoxicity or neurotoxicity • No hypertension • No signs of rejection • All labs remained within normal limits or not clinically significant / consistent with MMF use As of October 16, 2024. Source: Witkowski, IPITA 2024.
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