Technology transfer, process development and GMP manufacture of Eledon's allogeneic islet cell suspension. Prepared by Made Scientific for Eledon Pharmaceuticals.
Defy Limits. Deliver Results.
Eledon Pharmaceuticals × Made Scientific · ON 23715-2026 · Confidential, under mutual NDA
Start here
The program on one page
A summary of the proposal in the term sheet draft of 5 November 2026. Each panel links to the detail.
Carlos Candido and Laura Folk visited Princeton in the morning and East Norriton in the afternoon. On 16 September Chathuranga De Silva sent Eledon the agreed notes and action items.
20agreed actions, split across both teams
30 Sepeverything in the document lands by then
Octprocess development scope contracted
Novdevelopment work begins
Meeting context
The day covered the process walkthrough, organ logistics and scheduling, the Workstream 1 and Workstream 2 development designs, facility fit, and the commercial structure. The quality session was held over, to be covered on site with Made Scientific's Head of Quality.
What was agreed
Process development runs at Princeton, where the isolation train is qualified and the development team sits. Princeton is also the lead candidate for clinical supply.
The process needs 300 sq ft or more, with two Grade A biosafety cabinets and two to four operators. Princeton Suite 1 and Suite 3 were mapped against the process and confirmed to accommodate it with room to spare.
Made Scientific will hold a suite ready for the program and staff to peak demand, so the clinical baseline is never at risk. The commercial mechanism will be reflected in the term sheet.
CARR is the lead candidate to replace the COBE 2991. Cytiva Sepax C-Pro is retained as the contingency. Chorus is excluded, as it does not run density gradients.
A live COBE head-to-head baseline will be carried as a separately priced option, so the decision to run it can be taken on its regulatory merit.
Analytical method development is sequenced first, because it gates both the stability work and the separation optimization.
Three engineering runs form the base plan.
Eledon procures and owns the process equipment: one set for development, a second for GMP, plus an additional automated cell counter.
The engagement is structured as three agreements: the process development scope, Phase 3 clinical supply including PPQ, and commercial supply, which stays directional for now.
Since the visit. The term sheet draft of 5 November 2026 governs where it differs from these notes. Eledon has nominated the CARR UniFuge as the single separation platform, to be confirmed in the Development Agreement; Work Order 4.0 tests its feasibility and Eledon decides at Gate 1. The leading comparability approach is analytical comparability against Eledon's University of Chicago batch records, with a side-by-side COBE comparator only if the comparator decision, by 30 April 2027, calls for one. The engagement is documented in an MSA and Quality Agreement with separate Development, Clinical Supply, PPQ and Commercial Supply Agreements.
Set up the three-way non-disclosure agreement and call with CARR, including their application specialist.
Approach Cytiva on the Sepax C-Pro: whether a bespoke gradient protocol can be developed on the platform, and on what timeline.
Engage BioRep on the automated islet counter: their validation package, the method development scope, and the automated versus manual instrument versions.
Issue detailed, equipped floor plans for Princeton Suite 1 and Suite 3, laid out against the process: the two biosafety cabinets, the perfusion bench, incubator stacks, cell counter and separation platform.
Make the introduction to Made Scientific's Head of Quality and schedule the pre-award audit, offered at no charge for up to two days and two auditors.
By 30 September
Re-scope Workstream 1 around CARR with Sepax C-Pro as the contingency, including the design of experiments, the number of runs, and how each organ maps to each study so there is no dead time once material arrives.
Recommend the characterization panel Eledon asked for: flow cytometry to differentiate the fractions, identity by PCR, DNA content and oxygen consumption rate, and how each supports the correlation between incoming organ, process performance and clinical outcome.
Design the in-use stability arms to run off existing development runs rather than as standalone studies, covering both the 2–8 °C hold and the in-use condition after warming to room temperature.
Give a position on extractables and leachables: whether they are required for the BLA package, when they would need to start given a twelve to eighteen month run to validation, and the outsourcing route.
Issue a revised budgetary proposal with a defined go or no-go decision point for the University of Chicago license, and the fallback to the NIH CIT protocol built into the plan.
Provide directional commercial supply ranges, built upward from the CIT batch record, with proposed assumptions for the release failure rate and the commercial treatment of an attempt that does not release.
Review the public literature on islet cryopreservation to inform the scope of that option.
Eledon Pharmaceuticals
Week of 21 September
Send the updated upstream flow diagram following the clinical working session of 16 September, including the minimum pre-treatment duration.
Introduce Made Scientific to IIAM, so research-grade pancreas procurement can be set up in parallel with the commercial process.
Provide the CIT batch record materials list to support the bill of materials and the bottom-up costing.
By 30 September
Share the three to five year commercial ramp held in Eledon's model.
Confirm Eledon's position on a Type B meeting with the agency regarding the process change, and the expected timing.
Advise on progress and expected timing of the University of Chicago license, so the go or no-go date can be fixed in the plan.
October
Place the BioRep equipment order in October, for November arrival.
Confirm the lower dose threshold below which a lot would not be infused, once the clinical design settles.
Next sessions
Session
Purpose
Timing
Design of experiments working session
Firm up the Workstream 1 and 2 designs, the number of runs and the organ-to-study mapping, so the scope is mature before contracting.
Week of 21 September
Three-way call with CARR
Review the CARR dataset together and put questions to their application specialist.
To be scheduled
Commercial session
Directional commercial ranges and the shape of the clinical term sheet.
From 23 September
Quality session and pre-award audit
Held over from the site visit; to be covered on site with Made Scientific's Head of Quality.
To be scheduled
Key dates Eledon gave
When
What
Mid-October
Pancreas supply agreements in place.
October
Equipment ordered, for November arrival.
End October
Process development scope contracted, and term sheet signed for clinical manufacture.
November
Development work begins.
End 2026
Target for concluding the University of Chicago license.
As sent to Eledon on 16 September 2026 in the site visit follow-up. Progress on these items is tracked in the open items register and the next steps.
The agenda Chathuranga De Silva sent to Carlos Candido and Laura Folk on 14 September. Select a session to show the open items assigned to it.
Eledon Pharmaceuticals: Carlos Candido (Vice President, Cell Therapy Operations) and Laura Folk (Head of GMP Quality).
Made Scientific: Syed Husain (Chairman and Chief Executive Officer), Joseph Sinclair (Commercial), Chathuranga De Silva (Business Development), David Smith (Development and inbound technology transfer), Irving Ford (Quality and Compliance), Jesse O'Connor (Quality Operations and GMP Compliance), Jill Gliem (Technical Operations), Michelle Ng (Program Management) and Lee McDonald (Regulatory).
Overview
Program status
Eledon is moving the University of Chicago investigator-led islet program to a company-sponsored Phase 1/2/3 study and requires a CDMO to transfer, develop and manufacture the islet cell drug product. Tegoprubart is co-administered and is outside the scope of this program.
38research pancreata across Stage 1 and GMP readiness
Q1 2028first clinical attempt · planning case Q2 2028
48 hhold-time target · 96 h stretch
1 : 1one donor pancreas per batch
—items in the open items register
Eledon's responses of 1 September
Carlos Candido returned the Program Alignment Overview on 1 September with responses to thirteen of its points. Three of the responses changed the proposal. They are quoted verbatim below and in the sections they affect.
Introductions since 31 August.Global BioClinical, with which Made holds a master services agreement for donor tissue procurement under 21 CFR Part 1271, has connected the program to IIAM for research-grade whole pancreas, which the development work orders and engineering runs require. CARR Biosystems supplies the UniFuge single-use continuous-flow centrifuge that Made is installing at Princeton in Q4 2026; Eledon has nominated it as the single separation platform, and the three-way nondisclosure agreement among Made, Eledon and CARR Biosystems was executed in October 2026. Made has a commercial supply relationship with CARR Biosystems.
Clinical requirements
Requirements before the clinical campaign
On 14 August Eledon stated that cell separation and drug product stability must both be resolved before Phase 3 can proceed; the program is now planned as a Phase 1/2/3 study. It is sequenced around these two workstreams, each closed by a go/no-go gate that Eledon decides.
WS‑1Required
Automated gradient separation
Replace the discontinued COBE 2991 with a closed, commercially supported platform, the CARR UniFuge, and show that the product is comparable. The replacement requires method development as well as new equipment; see Separation.
Work orders
4.0 UniFuge set-up and feasibility · 5.0 screening, method lock and confirmation
Gate
Gate 1: UniFuge feasibility, against criteria both parties approve before the first run
Decision
Eledon's, at the end of Q2 2027
WS‑2Required
In-use stability
Extend the hold time from the approximately 6 to 12 h the academic process relies on to a validated 48 h target, with 96 h as the stretch target for fresh shipment nationwide; the 96 h arm runs by change order if Eledon elects it after the 48 h result. The study covers handling conditions only; the formulation does not change.
Work order
6.0 in-use stability and hold
Gate
Gate 2, Q4 2027: in-use stability against the 48 h target, and the status of the release methods
Shipments
Run by Eledon; qualified pack-outs prepared by Made
WS‑3Alongside Stage 1
Cryopreserved drug product
An in-process cryopreservation step developed alongside Stage 1, using islets from the development runs after their other uses and research pancreata dedicated to the study. Made's labor carries no separate fee; Eledon pays the study materials. It does not gate the clinical program.
Basis
Alongside Stage 1 · 2027
Acceptance
Agreed in the study protocol, for example post-thaw recovery, viability and GSIS against fresh controls
Risk
High; does not gate the clinical campaign
Timeline
Q4 2026 to the first clinical attempt
As proposed in the term sheet draft of 5 November 2026, the timeline runs from the binding term sheet, signed by 15 December 2026 with the deposit paid at signing and no later than 31 December 2026; Made Scientific starts set-up, technology transfer and procurement on receipt of the deposit, and the Development Agreement follows by 15 January 2027. Both required workstreams start on the CIT record and research pancreata. UniFuge work starts once the development isolation train is commissioned, the team is trained on the UniFuge under a named isolation lead, and CARR Biosystems' recipe and single-use sets arrive, planned for 15 January 2027. No activity in the first two quarters depends on the University of Chicago process or on Gate 1. The plan assumes about three suitable research pancreata a month with one process development team, and thirty-eight research pancreata across Stage 1 and GMP readiness.
By 15 Dec 2026Term sheet signed, with the deposit paid at signing and no later than 31 December 2026; Work Orders 1.0 to 3.0 start on receipt of the deposit. Development fees are firm for a term sheet signed by this date and a Development Agreement executed by 15 January 2027
By 15 Jan 2027Development Agreement and MSA executed and the pre-IND (Type B) meeting requested; the development isolation train is commissioned by 31 December 2026
By 30 Apr 2027Comparator decision, after the pre-IND meeting: a side-by-side COBE comparator only if needed
End Q2 2027Gate 1 at the close of Work Order 4.0: the UniFuge feasibility data. This decision sets the schedule; Work Order 5.0 starts only on Eledon's Notice to Proceed. The Clinical Supply Agreement is executed before Work Order 9.0
Q4 2027Gate 2 at the close of Work Order 6.0: in-use stability against the 48 h target and the status of the release methods. IND filed in October 2027
Q3 2027 to Q1 2028GMP readiness in the Grade B suite dedicated to the program: qualified suite and isolation train, approved batch record, three media fills and three engineering runs, closed by the GMP Readiness Review
Q1 2028First clinical attempt, provided both gates are passed (planning case Q2 2028). The Phase 1/2/3 campaign runs to about Q4 2029, with PPQ and BLA support in 2029 to 2030
Q1 2028 holds if the development train is commissioned by 31 December 2026, CARR Biosystems' recipe and sets arrive by 15 January 2027, three suitable research pancreata arrive each month and no step repeats; the planning case is Q2 2028. A side-by-side comparator or the Work Order 5.0 refinement stage would each add about two quarters, and more confirmation donors would add time. The BioRep equipment, with a lead time of 4 to 6 weeks, is not on the critical path.
Sites
Development and manufacture at Princeton
Process development is at Princeton: the development isolation train is commissioned and the team trained there under Work Order 3.0, and both required workstreams run on research pancreata. GMP work, from organ receipt, and Phase 1/2/3 clinical supply run in a Grade B process suite dedicated to the program at 201 College Road East (planned as Suite 3), with two Grade A biosafety cabinets that separate operators and process steps. The adjacent building at 307 College Road East would be the option for commercial supply after Phase 3. Made's East Norriton facility is not a manufacturing option for this program.
Princeton Suites 1–4 · proposed fit-outFour room layouts based on the facility drawings, shown in 3D with the proposed process equipment and the UniFuge in the separation position.
Five Grade B cleanroom suites, each with its own air handling unit and Grade A biosafety cabinets, and QC laboratories for environmental, microbial, in-process and release testing. Clinical supply: a Grade B process suite is dedicated to the program (planned as Suite 3), with two Grade A biosafety cabinets. The development isolation train, the UniFuge and the trained team are on site through Stage 1, and the GMP isolation train is qualified in the suite under Work Order 9.0; this is the basis of the Q4 2027 readiness date.
Process development laboratory where the Eledon-procured development isolation train is installed and commissioned (Work Order 3.0), and where the training block, WS‑1 and WS‑2 run. Closed-system platforms in inventory include Sepax C-Pro, CTS Rotea and LOVO; the CARR UniFuge arrives in Q4 2026.
The first FDA inspection at Princeton is expected in Q1 2027.
Princeton, New Jersey · adjacent to 201, on the same campus
A clear-span building on the same campus. Commercial option: the campus option for commercial supply after Phase 3. The commercial facility design package is an option, deferred at Eledon's request.
The same site team, quality system and QC laboratories as 201 College Road East, a short walk away.
Adjacentto 201, same campus
After Phase 3commercial supply option
In commissioning
East Norriton, Pennsylvania
2900 Potshop Lane
The classification plan includes a future manufacturing spine of eight process suites designed to Grade B, each with two Grade A biosafety cabinets and its own material and personnel airlocks between a supply corridor and a return corridor. The spine is unbuilt space today.
Rooms in commissioning around the bioreactor hall: process and flex rooms, cryogenic storage, LN2 tank storage and a cell bank room; material staging, a freezer farm and a media cold room; shipping and receiving with an inspection and laydown area, a cold box and a cold room.
Within the Philadelphia organ procurement corridor, one of the four catchments Eledon named along with New England, California and Chicago.
For this program: not a manufacturing option. Clinical supply is planned in a dedicated suite at Princeton.
Drag to pan, scroll or pinch to zoom, or use the buttons to move to an area. The drawing is the architectural classification plan issued for pricing. The eight-suite spine it shows is future build-out and is unbuilt space today.
Grade AGrade BGrade CGrade DCNCSource: Precis Engineering / DCI MacIntosh classification plan A-1011, preliminary, not for construction. The suite designation and organ path were shown for discussion on 15 September and are not a qualified route.
Princeton: 201 College Road East level 1 plan
Select the plan to open it full screen. The drawing is the level 1 material and personnel flow diagram of the operating building.
201 College Road East — level 1. Cleanroom suites CT 1–5 (rooms 738–743) on a
supply and return corridor pair, with airlocks, GMP storage, combination freezers and the QC laboratory
alongside; shipping, receiving, cold rooms and the warehouse to the east. Teal: cleanroom suites;
green: classified support areas; gray: controlled, not classified. Material and personnel flow diagram, level 1,
issued for review 2025.
Proposal
Work orders and scope
The term sheet sets out four stages. Stage 1, technology transfer and process development, comprises Work Orders 1.0 to 8.0A. Stage 2 is GMP readiness, Work Orders 7.0B to 12.0, followed by Phase 1/2/3 clinical supply per conforming lot against reserved capacity. Stage 3, PPQ and BLA support, and Stage 4, commercial supply with Made Scientific as primary US manufacturer, are documented in separate agreements executed before the PPQ campaign.
Fees. The term sheet draft of 5 November 2026 sets out the work orders, fees and payment terms, and supersedes the earlier proposals where they differ; it is listed under Documents. This page covers scope, schedule and terms, without fees. Since the September documents: the UniFuge, nominated by Eledon and to be confirmed in the Development Agreement, is the single separation platform, tested for feasibility in Work Order 4.0; the leading comparability approach is analytical comparability against Eledon's University of Chicago batch records, with a side-by-side COBE comparator only if elected; analytical work is split between methods for the study and the release strategy in Stage 1 (Work Orders 7.0A and 8.0A) and method and safety-test validation in GMP readiness (7.0B and 8.0B); a Work Order 5.0 refinement stage runs only if method screening calls for it and on Eledon's Notice to Proceed; and in-use stability draws on the Work Order 4.0 and 5.0 preparations rather than dedicated organs, with the 96-hour arm by change order.
Designs of experiments and organ use
The designs of experiments define Stage 1: what is run, on how many research pancreata, and which gate each study closes. Organ use is a major part of the pass-through estimate, so it is shown for each design.
Principal terms
The principal terms of the term sheet draft of 5 November 2026, without fees. The term sheet governs.
Gates and stops Gate 1, at the end of Q2 2027, reviews the UniFuge feasibility data from Work Order 4.0; Gate 2, in Q4 2027, reviews the in-use stability results against the 48-hour target and the status of the release methods. Each gate is reviewed against criteria, a statistical approach and a minimum number of evaluable runs that both parties approve before the first run, and Eledon elects to proceed, pause or stop within twenty business days. Work orders not started are not charged. Eledon may pause Stage 1 or GMP readiness on thirty days' notice; a pause of more than six months is a stop.
Payment structure A deposit due on signing of the term sheet and paid no later than 31 December 2026, with no further deposit at GMP readiness. 25% of each Stage 1 and GMP readiness work-order fee is invoiced as the work is done, with the deposit applied to the last of those invoices up to its amount; 75% is deferred to the earlier of thirty days after IND clearance and six months after the GMP Readiness Review, and any deposit remainder is credited against it. The deferral changes timing only. Materials and outsourced testing are passed through at cost plus 15%.
Clinical supply Phase 1/2/3 manufacture in the Dedicated Suite from the first clinical attempt, planned at up to 36 patients. A fee for each conforming lot; an attempt that does not produce one is charged a share of that fee by the point at which it stops, and a Made Scientific Failure carries no charge, with the next attempt performed once at no batch fee. A monthly reservation from the first attempt, less a credit for each lot, holds the suite, a named on-call roster and qualified materials for up to four attempts a month, in place of a minimum commitment. No reservation or standby fee applies before the first attempt; during the campaign, a standby fee replaces the reservation if no attempt starts for 90 days, unless Eledon has released the suite. Clinical prices are fixed through BLA filing.
Equipment Eledon procures and owns the process equipment: two isolation trains (one for development, one for GMP), the Ricordi chamber and an automated islet counter. Made Scientific installs, qualifies, calibrates and maintains it within its own GMP equipment program, with service contracts and spares funded by Eledon. The UniFuge is Made Scientific capital at no capital charge, with a back-up set before the first clinical attempt. A COBE 2991 is sourced only if an in-house side-by-side comparator is elected.
Intellectual property Results generated for the program belong to Eledon, including if manufacture later moves: the Product-specific process, data and specifications, including the purification method as applied to the Product, the locked UniFuge recipe (subject to CARR Biosystems' rights in the device) and the Product's cryopreservation process, together with the hold-time and stability data, the comparability data and the batch records. Made Scientific retains its background IP and know-how; the islet analytical panel methods are licensed to Eledon for the Product at no charge.
Commercial supply Made Scientific as PPQ manufacturer and primary US commercial manufacturer, supplying at least 60% of US commercial volume for five years from first commercial sale while it meets the agreed supply and quality terms, in dedicated capacity it funds with no capital charge to Eledon, subject to its capital approval before PPQ. The clinical batch fee carries into commercial supply, fixed to the third anniversary of first commercial sale and then indexed; minimum commitments and forecasting are set in the Commercial Supply Agreement.
Work Order 5.0 starts only on Eledon's Notice to Proceed at Gate 1. Pass-through costs are estimates until budgets are agreed in Work Order 1.0; spending more than 10% above an agreed budget needs Eledon's prior written approval. Program management, quality oversight and CMC support are provided with a named program manager at no separate charge through Stage 3. The Quality Agreement is executed before GMP-enabling work, and Eledon may audit before award at no charge. If the program stops, Eledon pays for work done and in process, its deferred fees included, and committed third-party costs, but not for work not started or any minimum.
Documents
Program documents
Program documents for Eledon’s donor-derived islet program. The term sheet of 5 November 2026 is a draft for discussion and supersedes the earlier proposals, including the term sheet of 9 October; each redline shows the changes. PDFs open in a new tab; the term sheets and the letter of intent are also available as Word downloads.
Term sheet and letter of intent, 5 November 2026
PDF
Term Sheet · V2 · 5 November 2026
Draft for discussion. The 9 October term sheet updated with the terms discussed on 4 November: development fees paid in part as the work is done and the rest deferred, the deposit, clinical supply, commercial supply and the joint press release.
Draft for discussion. A one-page, non-binding letter of intent with the principal terms ahead of the binding term sheet: scope, development fees, the deposit, clinical and commercial supply, termination, timeline and publicity.
Letter of intent signed by 16 November 2026. Eledon reviews the letter of intent and the term sheet draft of 5 November 2026; each has a redline against the earlier version under Documents. Questions to Joseph Sinclair at any time.
Term sheet signed by 15 December 2026, with the deposit paid at signing and no later than 31 December 2026. On receipt of the deposit Made Scientific starts set-up, technology transfer and procurement under Work Orders 1.0 to 3.0, and prepares the user requirement specifications for the isolation trains in Work Order 1.0, so that the equipment Eledon procures arrives to a specification Made will qualify.
Development isolation train commissioned by 31 December 2026, and research pancreas supply confirmed with IIAM against Eledon-set specifications, so that research pancreata are available for training, UniFuge feasibility and method development.
Eledon provides its University of Chicago manufacturing and release records by 31 December 2026 and requests the pre-IND (Type B) meeting by 15 January 2027; the comparator decision follows by 30 April 2027.
Development Agreement and MSA executed by 15 January 2027, confirming Eledon's election of the CARR UniFuge as the single separation platform. The Quality Agreement is negotiated in parallel and executed before GMP-enabling work (Work Order 9.0).
Eledon confirms the viability release method and the subsequent-dose minimum against the CIT specification it provided (open items 6 and 34).
Technical reference
The detail behind the proposal
Scope as understood, dose and campaign, the process by unit operation, separation, hold time, analytical methods, supply, photographs, the operating model, the capacity model, the published record and the basis of estimate.
Scope
Program scope as understood
Made Scientific's understanding of the program, set out so that any difference from Eledon's intent can be identified before it is priced.
Parameter
Made Scientific's understanding
Source
Drug product
Allogeneic islet cell suspension isolated from deceased-donor pancreas and infused fresh through the hepatic portal vein. Tegoprubart is co-administered and out of scope.
RFP deck
Dose
Initial dose 5,000 IEQ/kg; subsequent doses 4,500 IEQ/kg; IEQ varies from lot to lot. A batch is one attempt on one donor pancreas and yields at most one dose. Up to three procedures per patient, with approximately 25% of patients needing a second.
1 Sep
Clinical plan
A Phase 1/2/3 program on the NIH standard protocol, planned at up to 36 patients, with no control arm pending FDA alignment. The first clinical attempt is targeted for Q1 2028 and the campaign runs to about Q4 2029, with PPQ and BLA support in 2029 to 2030.
Term sheet; 14 Aug
Batch volume
The planning basis is 45 conforming lots for 36 patients, with one patient in four needing a second lot, and about 50 attempts at Eledon's planning failure rate of 10%, over about 24 months. At the published NIH CIT Consortium release rate of 52.5%, the same lots would take about 86 attempts over about 36 months. Made Scientific does not warrant a number of conforming lots; the University of Chicago release rate is open item 1.
Term sheet
Process basis
The NIH CIT Consortium master production batch record (SOP 3101 Rev 05): an executable batch record with process controls, sampling tables and a full reagent bill of materials, representing approximately 95% of current University of Chicago practice. Development does not depend on the University of Chicago agreement.
1 Sep
Processing envelope
Cold ischemia under 12 h from organ recovery. Receipt to static hold approximately 4 to 6 h, then a static hold of 24 to 48 h in a gas-permeable bag, with release testing before shipment. The CIT record cultures for 36 to 72 h (High Purity at 37 °C for the first 12 to 24 h, then 22 °C; Middle and Low at 22 °C) and sets a use-by time of 6 h after the bag is filled.
RFP deck; CIT record
Clinical organ supply
Sourced through organ procurement organizations under Eledon's relationships. Organ supply, rather than manufacturing capacity, limits commercial volume: approximately 2,500 organs a year today, potentially 4,000 with investment.
14 Aug
Research organ supply
IIAM whole pancreas, through Global BioClinical, within 1 to 2 days of request against Eledon-set specifications; clinical-grade organs at approximately one per week or better.
31 Aug
Matching
Blood type only; there is no HLA matching. Chain of identity runs from the donor identification number to the recipient's bag label. Made checks the donor's ABO group at receipt; recipient compatibility remains with Eledon and the clinical site.
14 Aug; term sheet
Sites
Process development in the Princeton process development laboratory. GMP work, from organ receipt, and clinical supply in a Grade B process suite dedicated to the program at 201 College Road East (planned as Suite 3), with two Grade A biosafety cabinets, the basis of the Q4 2027 readiness date. 307 College Road East would be the option for commercial supply after Phase 3. East Norriton is not a manufacturing option for this program.
Term sheet
Regulatory precedent
CellTrans LANTIDRA (donislecel-jujn), licensed in June 2023, has the same modality, source and route of administration. The Orphan Drug Designation on public record is for tegoprubart; the islet product's own designation status is open item 33.
Public
Dose and campaign
Dose and batch definitions
Two variables determine most of the commercial structure of the program: the quantity of product each patient requires, and the number of manufacturing attempts needed to deliver it. The calculators below can be adjusted.
Dose by body weight
Initial dose375,000IEQ · 5,000/kg
Subsequent dose337,500IEQ · 4,500/kg
300,000achievable IEQ range500,000
Within the achievable range.
Campaign: attempts required
Transplants required45doses delivered
Manufacturing attempts50at Eledon's planning failure rate of 10%, the term sheet's planning basis
The term sheet plans 45 conforming lots for 36 patients: about 50 attempts at Eledon's 10% failure rate, or about 86 at the published CIT release rate.
The defaults are the term sheet's planning basis: 36 patients, one in four needing a second lot, and Eledon's planning failure rate of 10%, giving 45 conforming lots in about 50 attempts. At the published NIH CIT Consortium rate (52.5% of 324 processed pancreata released a lot, 24.5% to 89.5% by center), the same lots take about 86 attempts; the University of Chicago rate is open item 1. Using the published 1.56 released lots per subject in place of one in four needing a second lot gives 56 lots. The term sheet prices clinical supply per conforming lot, with an attempt that does not produce one charged by the point at which it stops, and a monthly reservation from the first attempt, less a credit for each lot.
Process
The CIT process by unit operation
The NIH CIT Consortium master production batch record is the process basis for the transfer. Select a unit operation to see what the record specifies, Made Scientific's position, and the duration, staffing and release samples associated with it.
CIT recordMade Scientific positionDuration and staffing: Made planning estimateDevelopment workstream
Unit operations and both positions are taken from the Response to the RFP Deck issued on 14 September. Where Made Scientific's position has changed since, the term sheet draft of 5 November 2026 governs: Workstream 1 tests the CARR UniFuge as the single platform, with analytical comparability against Eledon's University of Chicago batch records as the leading approach, and Workstream 2 varies temperature and container at a fixed tissue density, with the 96-hour arm by change order. Durations are Made planning estimates for each section of the record (SOP 3101 Rev 05); the capacity model totals them across an attempt.
WS‑1 · Separation
Cell separation and purification
The COBE 2991 is being withdrawn. In Europe, the Middle East and Africa, orders closed in June 2023 and service ended in December 2025; in the United States, the last processing-set orders must be placed by 30 September 2028, and support ends in March 2031. Replacing it requires method development as well as new equipment, for the reasons set out in the batch record.
The CIT master batch record
Tissue is limited to 25 mL per run, so a large pancreas requires several runs.
Each run is collected into twelve fractions plus a wash fraction across a continuous density gradient.
The fractions are combined into three purity pools (High, Middle and Low), which are cultured separately and combined only when the infusion bags are filled.
The published work on purifying islets on a Sepax C-Pro (conference abstracts and a thesis from Lille) collects a single fraction, on a kit designed for mononuclear cells; seven human research pancreata split against the COBE gave comparable yield, purity and function. The constraint is the fraction architecture rather than the centrifugation: the downstream process depends on a three-pool collection that the replacement platforms have not yet demonstrated.
Twelve fractions combined into three purity pools, compared with a single-fraction collection.
Work Order 4.0: UniFuge set-up and feasibility
Eledon has nominated the CARR UniFuge as the single separation platform, to be confirmed in the Development Agreement. Work Order 4.0 starts once CARR Biosystems' recipe and single-use sets arrive, planned for 15 January 2027, and the team has been trained on the UniFuge in Work Order 3.0 under a named isolation lead. It runs six set-up cycles on surrogate beads with CARR Biosystems, then five whole-organ feasibility runs on research pancreata on one recipe, measuring every fraction, wash and residual, and post-culture recovery, viability, GSIS and tissue volume. The Gate 1 criteria cover usable recovery, projected settled tissue volume per bag at the target dose, mass balance, and closure and temperature control, and are signed by both quality units before the first run. The work order also delivers a patent landscape note for Eledon's freedom-to-operate determination, and ends at Gate 1 at the end of Q2 2027. The Gate 1 decision is Eledon's alone, and Work Order 5.0 starts only on Eledon's Notice to Proceed. The leading comparability approach compares the confirmation and engineering-run lots with Eledon's University of Chicago batch records and certificates of analysis; a side-by-side COBE comparator runs only if the comparator decision, made after the pre-IND meeting and by 30 April 2027, calls for one.
Platform
Status at Made
Role in Work Order 4.0
COBE 2991 Option
Only if a side-by-side comparator is elected
The device of the clinical reference process at the University of Chicago. A side-by-side comparator runs only if the comparator decision, by 30 April 2027, calls for one: preferably eight paired split digests at the University of Chicago, with Made Scientific's team and UniFuge on site; otherwise in house, on a unit Made sources. Not used as the clinical platform.
CARR Biosystems UniFuge
Installing Q4 2026
Single-use continuous-flow centrifuge nominated by Eledon. Islet purification on the UniFuge has not been demonstrated in the published literature; this work order determines whether it meets the criteria above. Made capital, available to the program at no capital charge; it stays in development through method confirmation and is then qualified in the GMP suite, with a back-up unit set before the first clinical attempt.
Large-bottle continuous gradient
Contingency
The published non-instrumented alternative to the COBE. In a small human comparison (a discontinuous bottle gradient, eight isolations against four on the COBE), yield and function were similar and purity was lower, without reaching significance. Not run in this work order. If the UniFuge does not meet the Gate 1 criteria, the parties agree a contingency path, which may be large-format continuous-gradient purification or a restarted design of experiments on an equivalent closed platform; it proceeds only on Eledon's Notice to Proceed, with Work Order 5.0, the second Work Order 6.0 study and Work Order 10.0 re-scoped by change order.
WS‑2 · Hold time
Hold time
In-use stability is the period from release to infusion, and each additional validated hour extends the distance the product can be shipped. The bar below uses the durations stated in Eledon's process description, with release on the Work Order 8.0A clock.
6–12 h today48 h target96 h stretch
Cold ischemia, <12 hReceipt to static hold, 4–6 hCulture, 24–48 hRelease, within 12 h (Work Order 8.0A)In-use period, release to infusion
Work Order 6.0: measurements and schedule
The licensed precedent has a six-hour shelf life at room temperature, and the best published 48-hour result is for islets held cold in preservation solution. The published literature points to three conditions that govern hold time: temperature, container gas permeability and tissue density in the bag. The study varies the first two, temperature (4, 15 and 22 °C, chamber-controlled) and container gas permeability, with time after fill (24, 48 and 72 h) as the response. Tissue density is fixed at the planned fill: dividing a research preparation into enough units to vary it would take each unit below the lowest density level in the design. The 96-hour arm is held until the 48-hour result is read and runs by change order if Eledon elects it. These are handling conditions, not formulation changes; culture remains as specified in the CIT record.
Container and closure assessment for the extended contact time. A 48-hour claim cannot rely on the six-hour rationale used for the licensed product. An outsourced extractables and leachables study is available as an option.
At each timepoint: viability, IEQ recovery read together with islet volume, morphology score, endotoxin and gram stain, with the full or reduced panel at each timepoint fixed in the protocol; GSIS stimulation index at 0 and 48 h. IEQ alone can mask fragmentation and central necrosis.
No dedicated organs: hold factors are read on the Work Order 4.0 feasibility preparations, then 48-hour full-bag holds on the Work Order 5.0 confirmation preparations after simulated shipment.
Pack-out design and six pack-outs for the mock shipments Eledon will run, with a temperature logger and a disposable indicator in each shipper. Each engineering run then places filled product on a formal in-use stability protocol, so that the shelf-life claim in the IND amendment is supported by GMP lots.
Analytical
Release testing
The safety panel is established and in routine GMP use at Made. The islet-specific methods are new to Made and require development and qualification in their own right: developed for the study in Work Orders 7.0A and 8.0A, then qualified and validated in Work Orders 7.0B and 8.0B.
Category
Parameter
Made position
Purity / identity
Islet volume, purity, morphology
Develop Automated islet counter methods qualified against the manual dithizone count; five of the twelve RFP parameters on one instrument
Purity / identity
Viability
Adapt SYTO 13 / ethidium bromide transferred and qualified, with a paired-stain bridge to the FDA/PI method in the CIT specification; an automated viability instrument trial is available as an option
Strength
Islet yield, IEQ
Develop Dose-critical; qualified to the 5,000 / 4,500 IEQ/kg basis
Strength
Glucose-stimulated insulin secretion
Develop The potency assay, developed in Work Order 7.0A, qualified to a stimulation-index specification before the first clinical lot and validated before PPQ (Work Order 7.0B); oxygen consumption rate and DNA on every lot, with samples retained
Safety
Endotoxin, sterility, mycoplasma
Established Endosafe, BacT/ALERT and BioFire in routine GMP use; validated for the islet product before the first clinical lot (Work Order 8.0B), with C. acnes and molds in the sterility panel and mycoplasma by NAT
Safety
Gram stain
Established Release test for transplant, per Eledon; compendial and rapid sterility reported after release
Characterization
Enzyme residuals
Develop Not defined in the RFP; the method follows the enzyme selection
CIT methods provided by Eledon
Eledon has provided the NIH CIT Consortium release specification for purified human pancreatic islets and three of the Consortium's analytical SOPs. Made will use them as the reference methods for the analytical transfer in Work Orders 7.0A and 8.0A. Where the proposal differs from them, the difference is noted below and listed in the open items.
Document
What it sets
Use in the program
Specification SOP 3100 A01 Rev 02
Product specification. Per bag: identity by visual inspection and dithizone; viability by FDA/PI of at least 70%; settled tissue at most 7.5 mL; sterility. Per infusion: dose of at least 5.0 × 10³ IEQ/kg for a first infusion and 4.0 × 10³ IEQ/kg for subsequent infusions; settled tissue at most 15 mL in total; purity of at least 20,000 IEQ per mL of settled tissue; endotoxin at most 5.0 EU/kg; gram stain; potency as a post-culture GSIS stimulation index above 1. In CIT-07, lots were released on an interim certificate of analysis, with GSIS and sterility reported after transplant.
Starting point for the phase-appropriate specifications in Work Order 7.0A. The subsequent-dose minimum of 4.0 × 10³ IEQ/kg is lower than Eledon's planned 4,500 IEQ/kg (open item 34).
Dithizone (DTZ) SOP 3104 A01
Islet identity, count and purity: IEQ conversion factors by diameter class, duplicate 100-microliter counts after purification and on the final product, purity estimated to the nearest 5%, and free versus trapped islets on at least 50 islets.
The manual count against which the automated islet counter is qualified (Work Order 7.0A) and validated under 21 CFR Part 11 (Work Order 7.0B). It remains the release and comparison count until the counter is validated.
Viability, FDA/PI SOP 3104 A02
Fluorescein diacetate and propidium iodide staining; 50 consecutive tissue particles scored for viable tissue, with the mean and standard deviation recorded on the worksheet (Attachment II).
The CIT release method for viability. The proposal transfers SYTO 13 / ethidium bromide, Eledon's current method, with a paired-stain bridge to FDA/PI. The release method is to be confirmed (open item 6).
Potency, GSIS SOP 3104 A03 Rev 03
400 IEQ per sample, one from the purest fraction before culture (cultured 12 to 24 hours, for information) and one from the post-culture High Purity product (for release); triplicate inserts of 100 IEQ; one hour at 2.8 mM glucose, then one hour at 28 mM; insulin by ELISA; stimulation index as the ratio of the two.
Basis of the potency assay developed in Work Order 7.0A. The sample requirement and timing are built into the release sampling plan in Work Order 8.0A.
Enzyme options and suppliers
The CIT batch record qualifies four enzyme options, with catalog numbers. The residuals method cannot be developed until the analyte is fixed, so the supplier selection in Work Order 2.0 determines an assay that must be qualified before process validation.
Supplier
Product
Catalog
SERVA / Nordmark
Collagenase NB1 GMP + Neutral Protease NB GMP
N0002937 / N0002936
SERVA / Nordmark
Collagenase NB1 Premium + Neutral Protease NB
17455 / 30301
VitaCyte
CIzyme Collagenase HA + CIzyme Thermolysin
001-1000 / 002-1000
Roche
Liberase MTF C/T GMP
05339880001
Equipment and supply
Materials and suppliers
Eledon procures and owns the process equipment: two BioRep isolation trains, one for development and one for GMP, the Ricordi chamber and an automated islet counter. The separation platform, the CARR UniFuge, is Made Scientific capital, tested for feasibility in Work Order 4.0. Two supplier introductions cover research organs and the separation platform.
Item
Responsibility
Position
BioRep Perfusion System
Eledon procures
Ductal enzyme perfusion. Lead time confirmed at 4 to 6 weeks. Two sets, one for development and one for GMP. Made prepares the user requirement specifications, receives and commissions the development set in Work Order 3.0, and qualifies the GMP set in the suite under Work Order 9.0.
BioRep Ricordi Isolator
Eledon procures
Controlled digestion at 32 to 38 °C, with dilution and collection at 30 °C or below. Two commissioning digestions on research pancreata before any development run.
BioRep Automated Islet Counter
Eledon procures
Supports five methods: volume, purity, morphology, IEQ and digestion cell count.
COBE 2991
Only if elected
For a side-by-side comparator only, if the comparator decision (by 30 April 2027) calls for one; the preferred route runs at the University of Chicago and needs no unit at Made. In house, Made sources a unit with a service plan; the unit, its processing sets and consumables are quoted and invoiced to Eledon as pass-through costs, and title passes to Eledon on payment. If no suitable unit is available on reasonable terms, Eledon procures one directly.
Separation platform
Gate 1, Q2 2027
The decision that sets the schedule, at the end of Q2 2027. The CARR UniFuge, nominated by Eledon, is tested for feasibility in Work Order 4.0; if it does not meet the Gate 1 criteria, the parties agree a contingency path. The UniFuge is Made capital, available to the program at no capital charge, with a back-up set before the first clinical attempt.
Research pancreata
IIAM via Global BioClinical
Whole pancreas within 1 to 2 days of request against Eledon-set specifications. An estimated thirty-eight organs across Stage 1 and GMP readiness: twenty-six in the work orders (commissioning, training and enzyme confirmation, UniFuge feasibility, method screening and confirmation, and engineering runs), six for enzyme-lot qualification and six replacements used only when a run is not evaluable; four more if the Work Order 5.0 refinement stage runs. Procured by Made through IIAM or another CRO and passed through at cost plus 15%. Per-lot enzyme qualification uses one organ for each new enzyme lot during the campaign. Each organ is screened against a research-organ specification (non-reactive serology required) and scored on a donor score, which is used as a covariate.
Clinical pancreata
Eledon
Through organ procurement organizations under Eledon's relationships; Made receives the organ at the dock.
Enzymes, gradient and culture media
Made
From the CIT bill of materials, with qualified lots held in date-controlled readiness. Estimated in the commercial summary and rebuilt from a bill of materials in Work Order 1.0.
Cleanrooms, cold chain, cryogenic storage
In place
Princeton infrastructure in routine use. Receipt of donor organs is a new workflow on existing infrastructure, qualified in Work Order 9.0.
The CIT batch record leaves the equipment, sterilized-item and disposables lists to each institution; Work Order 2.0 rebuilds the three lists (open item 7).
Princeton
Princeton facility photographs
Thirty-seven photographs of the operating facility at 201 College Road East: campus, cleanroom suites, QC and analytical laboratories, and development laboratories. Select a category, then an image to open it full screen.
Made Scientific, 201 College Road East, Princeton, New Jersey. Photographed 2025–2026.
Operating model
Organ receipt and on-call readiness
Organ availability cannot be scheduled, and a pancreas can arrive at any hour. The program therefore needs a staffing and on-call model rather than a production schedule.
Suite reservation. The Dedicated Suite, with dedicated incubators and cold storage, a named on-call roster with QA and QC cover, and qualified material lots, held for up to four non-overlapping attempts a month so that an accepted organ does not wait for a room. Charged monthly from the first attempt, less a credit for each lot, and never below zero in a month: the reservation covers readiness, and the batch fee covers each conforming lot. No reservation or standby fee applies before the first attempt.
On-call isolation team. A trained, named roster available at any hour during the campaign, ready at Made's dock by the later of six hours after notice of an accepted offer and the notified arrival time, with call-out and stand-down procedures. Readiness is covered by the monthly reservation; an offer canceled after call-out, or a pancreas declined at receipt, carries a small stop-point charge.
Standing materials. Qualified enzyme lots and gradient media held in date-controlled readiness, so that a batch does not wait for a reagent order.
Release on schedule. Fill is scheduled within the culture window so that release testing and QA disposition fall within staffed hours, with an interim certificate of analysis within eight hours of the release panel result.
Shift coverage. Princeton is extending its shift coverage.
Experience. Made Scientific has not previously performed human islet isolation. Its cleanroom, cold-chain and safety-testing infrastructure is established and in routine GMP use, and its team has commercial cell therapy launch and BLA inspection experience from other organizations. The first work orders therefore build the capability on the CIT record using research pancreata, and each GMP commitment follows a gate that Eledon reviews. Eledon is invited to conduct a pre-award audit at no charge.
Capacity model: organ offers, the reserved suite and the clinical campaign
A pancreas arrives unscheduled, so the campaign is paced by organ offers rather than by a calendar. Starting from the reservation terms, the model calculates how many acceptable offers the campaign needs, how many arrive while the suite is still within its processing window, and the resulting load on the suite, the on-call team and QC.
Embedded model. Press p inside it for presentation mode and r to reset.Open full screen
All figures are calculated from the proposed reservation terms, the campaign calculator in the Dose section and the CIT record. Offers are counted after donor acceptance; an offer is declined only when every suite is within its processing window. This is a planning model for discussion, not a capacity commitment.
Published record
Published literature and regulatory record
The proposal is based on the public manufacturing, regulatory and stability record for donor-derived islets: the NIH CIT Consortium manufacturing paper and SOPs, the LANTIDRA summary basis for approval and label, the FDA islet guidance, and the literature on isolation, hold time, shipping, potency and cryopreservation. Bracketed numbers match the citations in the DOE plans and the proposal documents of 14 September.
Release rate Across the NIH CIT Consortium centers, 324 pancreata produced 170 released lots (52.5%, ranging from 24.5% to 89.5% by center), and insufficient islet mass was the most common reason for failure. CIT-07 used 1.56 released lots per subject. For these reasons the term sheet charges an attempt that does not produce a conforming lot by the point at which it stops, and plans 45 conforming lots in about 50 attempts, which at the published rate would take about 86; Work Order 2.0 sets a donor acceptance specification and an offer-screening score. [1, 6, 7, 8, 9]
The licensed precedent LANTIDRA is released with a six-hour shelf life at room temperature and carried from the manufacturing suite to the clinic in the same building. FDA approved it with the extractables and leachables study report left to a post-marketing commitment, on the rationale of 510(k)-cleared bags and six-hour storage; the BLA had earlier received a complete response letter citing facility observations, reagent qualification, release testing and quality staff training. No 48-hour claim has been approved to date, and the readiness assessment addresses each of those findings. [53, 54, 55]
Hold time The best published 48-hour result is for islets held cold in preservation solution (<5% loss at 4 °C compared with 19% at 22 °C). Gas-permeable vessels outperformed non-permeable bags over a 48-hour, 11,000 km shipment, although the UK clinical validation shipped in standard transfusion bags with no loss of function. Cultured islets ship better than fresh islets, and drops to 15 °C or below were the most common temperature excursion in shipping. Workstream 2 therefore varies temperature and container as well as time. [10, 11, 12, 13, 14, 15, 16]
Replacing the COBE 2991 The COBE is being withdrawn: orders closed in Europe, the Middle East and Africa in June 2023, and in the United States the last processing-set orders must be placed by 30 September 2028, with support ending in March 2031. On a commercial closed processor, human islet purification has been reported on the Sepax C-Pro, in conference abstracts and a thesis from Lille: seven research pancreata split against the COBE gave comparable yield, purity and function, with a single fraction per run and a pending patent application. Large-bottle gradients are the published non-instrumented alternative. Purification is run cold, because rotor friction takes an uncooled bowl above 20 °C. [17, 18, 19, 57, 58, 59, 60]
Enzyme In 251 Edmonton isolations the supplier's Wünsch units did not predict outcome. An in-house class II / class I collagenase ratio did, with 8.7 times higher odds of success below a ratio of 0.204, and protease dose per gram was the other determinant. CIT-07 used three blends across 75 lots with no difference in IEQ per gram, and the field has already lost its standard enzyme once. The proposal therefore includes in-house per-lot qualification and a named second source. [1, 23, 24, 25, 26]
Tissue volume and rescue CIT limited the infusion to 7.5 mL of tissue per bag and 15 mL per infusion; the licensed label limits it to 10 cc. CIT-07 needed one to four COBE runs per pancreas. Edmonton prevented portal vein thrombosis in its most recent 101 procedures by limiting packed cell volume to under 5 mL, with therapeutic heparin and ablation of the catheter tract, and a team in Gdansk, working with Chicago and Miami, reduced a 504,000-IEQ preparation from 24.6 to 11.6 mL by unit-gravity sedimentation, keeping 374,940 IEQ. Tissue volume is a primary response in Work Order 5.0, and a rescue purification route is qualified. [1, 20, 21, 22, 54]
Quality control The automated islet counter correlated with trained manual counting at r = 0.78 (slope 1.02), so the manual dithizone count remains the release method until the counter method is qualified. Oxygen consumption rate dose (rate per DNA multiplied by the islet dose) predicted insulin independence after 13 first transplants, where GSIS and membrane-integrity stains did not; it is the alternative potency option. In a 452-pancreas series, 64% of preservation fluids were culture-positive; the preservation fluid is therefore cultured at receipt, and a fresh-product release procedure is written before the first engineering run. [27, 28, 29, 32, 33, 34, 35]
Cryopreservation Conventional slow-freeze cryopreservation has a long record of poor recovery. Vitrification with optimized loading and rewarming kept human islet viability at 87% of fresh controls, with normal glucose-stimulated insulin secretion in vitro; viability held over nine months of storage in mouse and stem-cell-derived islets, and function in vivo was shown with mouse, porcine and stem-cell-derived islets. Workstream 3 develops an in-process cryopreservation step alongside Stage 1, screening this route with conventional methods; it does not gate the clinical campaign. [36, 37, 38]
Reference list: 55 sources, numbered as in the documents of 14 September
[1] Ricordi C, Goldstein JS, Balamurugan AN, et al. National Institutes of Health-Sponsored Clinical Islet Transplantation Consortium Phase 3 Trial: Manufacture of a Complex Cellular Product at Eight Processing Facilities. Diabetes 2016;65(11):3418-3428. PMID 27465220. PMC5079635. doi:10.2337/db16-0234.
[2] NIH CIT Consortium Chemistry Manufacturing Controls Monitoring Committee. Purified Human Pancreatic Islets (PHPI) Master Production Batch Record: A Standard Operating Procedure of the NIH Clinical Islet Transplantation Consortium. CellR4 Repair Replace Regen Reprogram 2014;2(2):e891. PMID 30581890. PMC6300133.
[4] NIH CIT Consortium Chemistry Manufacturing Controls Monitoring Committee. Purified Human Pancreatic Islets, Certificate of Analysis (Product Code PHPI-A-01): Standard Operating Procedure of the NIH Clinical Islet Transplantation Consortium. CellR4 Repair Replace Regen Reprogram 2015;3(1):e1448. PMID 30613703. PMC6319623.
[5] NIH CIT Consortium Chemistry Manufacturing Controls Monitoring Committee. Purified Human Pancreatic Islet - Viability Estimation of Islet Using Fluorescent Dyes (FDA/PI): Standard Operating Procedure of the NIH Clinical Islet Transplantation Consortium. CellR4 Repair Replace Regen Reprogram 2015;3(1):e1378. PMID 30613700. PMC6319380.
[6] Hering BJ, Clarke WR, Bridges ND, et al. Phase 3 Trial of Transplantation of Human Islets in Type 1 Diabetes Complicated by Severe Hypoglycemia. Diabetes Care 2016;39(7):1230-40. PMID 27208344. PMC5317236. doi:10.2337/dc15-1988.
[7] Balamurugan AN, Naziruddin B, Lockridge A, et al. Islet product characteristics and factors related to successful human islet transplantation from the Collaborative Islet Transplant Registry (CITR) 1999-2010. Am J Transplant 2014;14(11):2595-606. PMID 25278159. PMC4282081. doi:10.1111/ajt.12872.
[8] Wang LJ, Kin T, O'Gorman D, et al. A Multicenter Study: North American Islet Donor Score in Donor Pancreas Selection for Human Islet Isolation for Transplantation. Cell Transplant 2016;25(8):1515-1523. PMID 26922947. PMC5167495. doi:10.3727/096368916X691141.
[9] Kaddis JS, Danobeitia JS, Niland JC, et al. Multicenter analysis of novel and established variables associated with successful human islet isolation outcomes. Am J Transplant 2010;10(3):646-56. PMID 20055802. PMC2860018. doi:10.1111/j.1600-6143.2009.02962.x.
[10] Noguchi H, Naziruddin B, Jackson A, et al. Low-temperature preservation of isolated islets is superior to conventional islet culture before islet transplantation. Transplantation 2010;89(1):47-54. PMID 20061918. doi:10.1097/TP.0b013e3181be3bf2.
[11] Ichii H, Sakuma Y, Pileggi A, et al. Shipment of human islets for transplantation. Am J Transplant 2007;7(4):1010-20. PMID 17391141. doi:10.1111/j.1600-6143.2006.01687.x.
[12] Kitzmann JP, Pepper AR, Gala-Lopez B, et al. Human islet viability and function is maintained during high-density shipment in silicone rubber membrane vessels. Transplant Proc 2014;46(6):1989-91. PMID 25131090. PMC4169700. doi:10.1016/j.transproceed.2014.06.002.
[13] Ikemoto T, Matsumoto S, Itoh T, et al. Assessment of islet quality following international shipping of more than 10,000 km. Cell Transplant 2010;19(6):731-41. PMID 20525435. doi:10.3727/096368910X508834.
[14] Kaddis JS, Hanson MS, Cravens J, et al. Standardized transportation of human islets: an islet cell resource center study of more than 2,000 shipments. Cell Transplant 2013;22(7):1101-11. PMID 22889479. PMC3745279. doi:10.3727/096368912X653219.
[15] Olack BJ, Alexander M, Swanson CJ, et al. Optimal Time to Ship Human Islets Post Tissue Culture to Maximize Islet. Cell Transplant 2020;29:963689720974582. PMID 33231091. PMC7885128. doi:10.1177/0963689720974582.
[16] Aldibbiat A, Huang GC, Zhao M, et al. Validation of Islet Transport From a Geographically Distant Isolation Center Enabling Equitable Access and National Health Service Funding of a Clinical Islet Transplant Program for England. Cell Med 2012;2(3):97-104. PMID 27004135. PMC4776046. doi:10.3727/215517911X617905.
[17] Buemi A, Mouard NI, Darius T, et al. Continuous vs. discontinuous purification of isolated human islets: functional and morphological comparison. Front Endocrinol (Lausanne) 2023;14:1195545. PMID 37455917. PMC10348810. doi:10.3389/fendo.2023.1195545.
[18] Noguchi H. Pancreatic Islet Purification from Large Mammals and Humans Using a COBE 2991 Cell Processor versus Large Plastic Bottles. J Clin Med 2020;10(1):10. PMID 33374512. PMC7793136. doi:10.3390/jcm10010010.
[19] Miyagi-Shiohira C, Kobayashi N, Saitoh I, et al. The Evaluation of Islet Purification Methods That Use Large Bottles to Create a Continuous Density Gradient. Cell Med 2017;9(1-2):45-51. PMID 28174674. PMC5225677. doi:10.3727/215517916X693131.
[20] Gołębiewska JE, Gołąb K, Gorycki T, et al. "Old School" Islet Purification Based on the Unit Gravity Sedimentation as a Rescue Technique for Intraportal Islet Transplantation-A Case Report. Cell Transplant 2020;29:963689720947098. PMID 32749147. PMC7563026. doi:10.1177/0963689720947098.
[21] Matsumoto S, Takita M, Shimoda M, et al. Impact of tissue volume and purification on clinical autologous islet transplantation for the treatment of chronic pancreatitis. Cell Transplant 2012;21(4):625-32. PMID 22305295. PMC4070319. doi:10.3727/096368911X623899.
[22] Kawahara T, Kin T, Kashkoush S, et al. Portal vein thrombosis is a potentially preventable complication in clinical islet transplantation. Am J Transplant 2011;11(12):2700-7. PMID 21883914. PMC3226916. doi:10.1111/j.1600-6143.2011.03717.x.
[23] Kin T, Zhai X, Murdoch TB, et al. Enhancing the success of human islet isolation through optimization and characterization of pancreas dissociation enzyme. Am J Transplant 2007;7(5):1233-41. PMID 17359501. doi:10.1111/j.1600-6143.2007.01760.x.
[24] Balamurugan AN, Loganathan G, Bellin MD, et al. A new enzyme mixture to increase the yield and transplant rate of autologous and allogeneic human islet products. Transplantation 2012;93(7):693-702. PMID 22318245. PMC3314155. doi:10.1097/TP.0b013e318247281b.
[25] Brandhorst H, Friberg A, Nilsson B, et al. Large-scale comparison of Liberase HI and collagenase NB1 utilized for human islet isolation. Cell Transplant 2010;19(1):3-8. PMID 19818208. doi:10.3727/096368909X477507.
[26] O'Gorman D, Kin T, Imes S, et al. Comparison of human islet isolation outcomes using a new mammalian tissue-free enzyme versus collagenase NB-1. Transplantation 2010;90(3):255-9. PMID 20463640. doi:10.1097/TP.0b013e3181e117ce.
[27] Barnett MJ, McGhee-Wilson D, Shapiro AM, et al. Variation in human islet viability based on different membrane integrity stains. Cell Transplant 2004;13(5):481-8. PMID 15565860. doi:10.3727/000000004783983701.
[28] Buchwald P, Bernal A, Echeverri F, et al. Fully Automated Islet Cell Counter (ICC) for the Assessment of Islet Mass, Purity, and Size Distribution by Digital Image Analysis. Cell Transplant 2016;25(10):1747-1761. PMID 27196960. doi:10.3727/096368916X691655.
[29] Kissler HJ, Niland JC, Olack B, et al. Validation of methodologies for quantifying isolated human islets: an Islet Cell Resources study. Clin Transplant 2010;24(2):236-42. PMID 19719726. PMC3166241. doi:10.1111/j.1399-0012.2009.01052.x.
[30] Kin T, Senior P, O'Gorman D, et al. Risk factors for islet loss during culture prior to transplantation. Transpl Int 2008;21(11):1029-35. PMID 18564983. doi:10.1111/j.1432-2277.2008.00719.x.
[31] Kerr-Conte J, Vandewalle B, Moerman E, et al. Upgrading pretransplant human islet culture technology requires human serum combined with media renewal. Transplantation 2010;89(9):1154-60. PMID 20098354. doi:10.1097/TP.0b013e3181d154ac.
[32] Meier RPH, Andrey DO, Sun P, et al. Pancreas preservation fluid microbial contamination is associated with poor islet isolation outcomes - a multi-centre cohort study. Transpl Int 2018;31(8):917-929. PMID 29603452. doi:10.1111/tri.13159.
[33] Sweet IR, Gilbert M, Scott S, et al. Glucose-stimulated increment in oxygen consumption rate as a standardized test of human islet quality. Am J Transplant 2008;8(1):183-92. PMID 18021279. doi:10.1111/j.1600-6143.2007.02041.x.
[34] Kitzmann JP, O'Gorman D, Kin T, et al. Islet oxygen consumption rate dose predicts insulin independence for first clinical islet allotransplants. Transplant Proc 2014;46(6):1985-8. PMID 25131089. PMC4170186. doi:10.1016/j.transproceed.2014.06.001.
[35] Hanson MS, Park EE, Sears ML, et al. A simplified approach to human islet quality assessment. Transplantation 2010;89(10):1178-88. PMID 20182409. PMC2948961. doi:10.1097/TP.0b013e3181d54bce.
[36] Zhan L, Rao JS, Sethia N, et al. Pancreatic islet cryopreservation by vitrification achieves high viability, function, recovery and clinical scalability for transplantation. Nat Med 2022;28(4):798-808. PMID 35288694. PMC9018423. doi:10.1038/s41591-022-01718-1.
[37] Kojayan GG, Alexander M, Imagawa DK, et al. Systematic review of islet cryopreservation. Islets 2018;10(1):40-49. PMID 29315020. PMC5800373. doi:10.1080/19382014.2017.1405202.
[38] Chen AR, Chansky J, Burke JA. Long-term storage, cryopreservation, and culture of isolated human islets: a systematic review. Front Transplant 2025;4:1614849. PMID 40860015. PMC12370674. doi:10.3389/frtra.2025.1614849.
[39] Markmann JF, Rickels MR, Eggerman TL, et al. Phase 3 trial of human islet-after-kidney transplantation in type 1 diabetes. Am J Transplant 2021;21(4):1477-1492. PMID 32627352. PMC9074710. doi:10.1111/ajt.16174.
[40] Berney T, Andres A, Bellin MD, et al. A Worldwide Survey of Activities and Practices in Clinical Islet of Langerhans Transplantation. Transpl Int 2022;35:10507. PMID 36033644. PMC9402897. doi:10.3389/ti.2022.10507.
[41] Bertuzzi F, De Carlis LG. Human Pancreatic Islet Production: From Research Protocols to Standardized Multicenter Manufacturing. Diabetes 2016;65(11):3243-3245. PMID 27959861. doi:10.2337/dbi16-0045.
[48] Witkowski P, Philipson LH, Kaufman DB, et al. The demise of islet allotransplantation in the United States: A call for an urgent regulatory update. Am J Transplant 2021;21(4):1365-1375. PMID 33251712. PMC8016716. doi:10.1111/ajt.16397.
[49] Wang Y, McGarrigle J, Cook J, et al. The future of islet transplantation beyond the BLA approval: challenges and opportunities. Front Transplant 2025;4:1522409. PMID 40124184. PMC11925927. doi:10.3389/frtra.2025.1522409.
[50] Giri O, Goldman JD. Donislecel: First Cellular Therapy to Treat Patients With Brittle Type 1 Diabetes. Clin Diabetes 2024;42(2):337-340. PMID 38694249. PMC11060608. doi:10.2337/cd23-0091.
[51] Barshes NR, Lee T, Goodpasture S, et al. Achievement of insulin independence via pancreatic islet transplantation using a remote isolation center: a first-year review. Transplant Proc 2004;36(4):1127-9. PMID 15194393. doi:10.1016/j.transproceed.2004.04.057.
[52] Kempf MC, Andres A, Morel P, et al. Logistics and transplant coordination activity in the GRAGIL Swiss-French multicenter network of islet transplantation. Transplantation 2005;79(9):1200-5. PMID 15880070. doi:10.1097/01.tp.0000161224.67535.41.
[53] US Food and Drug Administration, Center for Biologics Evaluation and Research. Summary Basis for Regulatory Action — LANTIDRA (donislecel-jujn), BLA 125734. 28 June 2023. https://www.fda.gov/media/170457/download
[54] LANTIDRA (donislecel-jujn) allogeneic pancreatic islet cellular suspension for hepatic portal vein infusion — US prescribing information. CellTrans Inc., June 2023. https://www.fda.gov/media/169920/download
[55] US Food and Drug Administration, CBER. Clinical review memorandum, LANTIDRA (donislecel-jujn), BLA 125734. 2023. https://www.fda.gov/media/170827/download
[56] US Food and Drug Administration. Guidance for industry: considerations for allogeneic pancreatic islet cell products. September 2009. https://www.fda.gov/media/77497/download
[57] Kerr-Conte J, Menasria N, Pasquetti G, et al. Alternative method for human islet purification using Sepax. Abstract 06-1, IPITA 2025 Congress. Transplantation 2025;109(6S1):26. https://doi.org/10.1097/01.tp.0001123028.17700.6f
[58] Menasria N, Quenneville S, Delalleau N, et al. SEPAX–SEFIA, a repurposed closed system for human islet purification and processing in a cGMP environment. Abstract 235.5, IPITA–IXA–CTRMS 2023 Joint Congress. Transplantation 2023;107(10S2):65. https://doi.org/10.1097/01.tp.0000994100.40609.d5
[59] Menasria N. Islet cell purification systems: integration of novel repurposed GMP closed-system technologies from evaluation to patent implementation. PhD thesis, Université de Lille, 2024. https://theses.hal.science/tel-05677212
[60] AABB. Information for COBE 2991 discontinuation, and Association Bulletin #25-02, 19 December 2025. https://www.aabb.org/blood-biotherapies/blood/transfusion-medicine/transfusion-medicine-resources/information-for-cobe-2991-discontinuation. Terumo BCT. COBE 2991: disposable-set ordering and support dates. https://www.terumobct.com/en/na/products-services/cell-therapy-technologies/cell-therapy-technologies-products/cobe-2991.html
[65] Integrated Islet Distribution Program, City of Hope. Human islets for research — islet handling tips and investigator standard operating procedures. https://iidp.coh.org/SOPs/Investigator-Policies-Standard-Operating-Procedures
Assumptions
Basis of estimate
What the estimate assumes, and what it leaves out.
Assumed
One donor pancreas processed into one patient dose and released fresh, at the hold condition established in Workstream 2. An attempt is one GMP manufacturing attempt on one donor pancreas; a conforming lot meets the approved specification for its intended recipient.
Eledon procures and owns the process equipment: two BioRep isolation trains, the Ricordi chamber and an automated islet counter. Made specifies, receives, installs, qualifies and maintains it, and provides the UniFuge at no capital charge. A COBE 2991 is sourced only if an in-house side-by-side comparator is elected. Capital equipment is excluded from the totals.
Research pancreata through IIAM or another CRO: thirty-eight across Stage 1 and GMP readiness, including six replacements used only when a run is not evaluable, and four more if the Work Order 5.0 refinement stage runs, at cost plus 15%. Clinical procurement, OPO contracting and the donor-eligibility determination are Eledon's responsibility.
The CIT record is the process basis; differences in University of Chicago practice are applied when they are received.
Clinical supply follows the term sheet's planning basis: 36 patients, 45 conforming lots and about 50 attempts over about 24 months from the first attempt in Q1 2028, with no control arm. The Q4 2027 readiness date assumes the Grade B suite dedicated to the program at 201 College Road East; 307 College Road East would be the option for commercial supply after Phase 3.
Gram stain at release, with compendial and rapid sterility reported after release, subject to CBER agreement.
An in-process cryopreservation step is developed alongside Stage 1; it does not gate the clinical program.
Excluded
Commercial supply volumes, minimum commitments and forecasting, which the Commercial Supply Agreement sets; negotiation begins at Eledon's request, expected in late 2027 or early 2028.
Stem-cell-derived or iPSC islet programs.
The optional services in the term sheet, including a side-by-side COBE comparator, the Work Order 5.0 refinement stage, the University of Chicago reverse person-in-plant and the commercial facility design package.
Clinical site logistics beyond the qualified pack-out.
Regulatory filing fees and CMC authoring by Eledon.
PDF
PDF
PDF
PDF
PDF
PDF
PDF
