Cadaveric Islet Cell Program · Eledon × Made Scientific

Overview

Where this program stands

Eledon is converting the University of Chicago investigator-led islet program into a company-sponsored registrational study and needs a CDMO to transfer, develop and manufacture the islet cell drug product. Tegoprubart is co-administered and out of scope.

—Phase 1 indicative budget

Q1 2028first GMP batch available

48 hhold-time target · 96 h stretch

1 : 1one pancreas, one dose

—register items for 15 September

What changed on 1 September

Carlos Candido returned the Program Alignment Overview with responses to thirteen of its points. Three of them changed the shape of the proposal. They are quoted here exactly as written, and again wherever they apply below.

Two 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, the supply every development work order depends on. And CARR Biosystems, whose UniFuge single-use continuous-flow centrifuge Made is installing at Princeton this quarter, enters the separation-platform screen as a candidate for the COBE replacement. Neither is a commitment on Eledon's behalf; both are available to Eledon.

Must-haves

The two things that gate Phase 3

Eledon was unambiguous on 14 August: cell separation and drug product stability must both be solved before Phase 3 can proceed. Everything here is sequenced behind that.

WS‑1Must-have

Automated gradient separation

Replace the discontinued COBE 2991 with a closed, commercially supported platform that is non-inferior to COBE at minimum. Not a like-for-like swap — see Separation.

Work orders: 4.0 screen · 5.0 method & bridge
Gate: Purity and IEQ recovery vs COBE baseline
Decision: Platform selected Q2 2027

WS‑2Must-have

In-use stability

Extend hold time from the ~6–12 h the academic process relies on to a validated 48 h target, with 96 h as the stretch that opens nationwide fresh shipping. Hold time only — no formulation change.

Work order: 6.0 hold-time DOE
Gate: 48 h viability, IEQ and GSIS in spec
Split: Eledon ships, Made packs out

WS‑3Parallel option

Cryopreserved drug product

DMSO, DMSO-free and hydrogel approaches screened, controlled-rate freeze profile, post-thaw recovery and potency. Priced as an option outside the Phase 1 total, and explicitly not permitted to gate the clinic.

Basis: Option · 12–18 months
Gate: Post-thaw IEQ recovery, GSIS >1
Risk: High — non-gating by design

Understanding

Program as we understand it

Restated in our own words, so any gap between what Eledon means and what Made has heard is visible before it is priced.

Parameter	Our understanding	Source
Drug product	Allogeneic islet cell suspension isolated from deceased-donor pancreas; infused fresh via the hepatic portal vein. Tegoprubart co-administered, out of scope.	RFP deck
Dose	Initial dose 5,000 IEQ/kg; subsequent doses 4,500 IEQ/kg; IEQ variable lot to lot. One donor pancreas yields one dose; up to three procedures per patient, ~25% needing a second.	1 Sep
Clinical plan	Direct to Phase 3 on the NIH standard protocol; 24 patients baseline, no control arm pending FDA alignment. Phase 3 start targeted end 2027; BLA 2029; launch 2030.	14 Aug
Batch volume	~50–75 batches through the BLA. 24 patients plus ~25% second transplants is ~30 transplants; the remainder is Phase 1/2 material, engineering and PPQ runs, or attempts that do not reach a transplantable dose.	Both
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, and ~95% of current University of Chicago practice. Development is not gated on the Chicago agreement.	1 Sep
Processing envelope	Cold ischemia <12 h from harvest. Receipt to static hold ~4–6 h. Purified islets culture 24–48 h — High Purity at 37 °C, Middle and Low at 22 °C — with release testing over a further 24–48 h before fresh shipment.	CIT record
Clinical organ supply	Sourced via organ procurement organizations under Eledon's relationships. Supply, not manufacturing capacity, is the commercial ceiling — ~2,500 organs a year today, potentially 4,000 with investment.	14 Aug
Research organ supply	IIAM whole pancreas, connected through Global BioClinical, within 1–2 days of request against Eledon-set specifications; clinical grade at ~1 per week or better.	31 Aug
Matching	Blood type only. No HLA matching, so chain of identity is an ABO confirmation at release.	14 Aug
Sites	Process development at Princeton. Made proposes East Norriton for Phase 3 clinical supply, in a dedicated Grade B suite; the decision is Eledon's after 15 September.	Proposal
Regulatory precedent	CellTrans LANTIDRA (donislecel-jujn), licensed June 2023 — same modality, source and route. Orphan Drug Designation granted for the Eledon program.	Public

Dose & campaign

What a dose is, and what a batch is

Two questions decide most of the commercial shape of this program: how much product a patient needs, and how many manufacturing attempts it takes to deliver it. Move the inputs and see.

Dose — weight-indexed

Recipient body weight 75 kg

Initial dose375,000IEQ · 5,000/kg

Subsequent dose337,500IEQ · 4,500/kg

Within the achievable band.

Campaign — attempts required

Phase 3 patients 24

Needing a second transplant 25%

Non-conforming isolation rate 0%

Ph 1/2, engineering and PPQ runs 0

Transplants required30doses delivered

Manufacturing attempts30at a 0% non-conforming rate

Phase 2 at the proposal's batch price—

Against the stated 50–75 batch range.

The non-conforming rate defaults to zero because the rate is not known — it is register item 1. Every other input above is taken from the RFP deck or from Eledon's own answers. The Phase 2 figure is the proposal's batch price times attempts, plus the 24-month reservation, the PPQ campaign and method validation.

WS‑1

Cell separation is an architecture problem

The COBE 2991 is discontinued — orders closed June 2023, service sunset December 2025. Replacing it is not an equipment swap, and the batch record shows why.

What the CIT batch record actually does

Tissue is capped at 25 mL per run — a large pancreas needs several runs.
Each run is collected into twelve fractions plus a wash fraction, across a continuous density gradient.
Those fractions are assembled into three purity pools — High, Middle and Low — which are then cultured and released separately.

The published proof-of-concept for running islets on a Sepax or Sefia platform collects a single fraction, on a kit designed for mononuclear cells, and reports 75% purity from one human pancreas. The gap is not centrifugation. It is that the downstream process depends on a fraction architecture the replacement does not yet have.

Comparison of the COBE 2991 twelve-fraction collection feeding three purity pools against a single-fraction collection — Twelve fractions into three purity pools, against a single-fraction collection.

The platform screen — work order 4.0

Four candidates run against a COBE baseline on split digests, with the criteria fixed in advance: purity and IEQ recovery non-inferior to COBE, viability, fraction resolution, tissue-volume ceiling, closure and commercial support. Roughly eight research pancreata; a decision report with the platform's lead time; the first go / no-go gate.

Platform	Status at Made	Why it is in the screen
COBE 2991 Baseline	To be sourced, refurbished	The comparability reference, per Eledon. Establishes the twelve-fraction, three-pool baseline the candidates are measured against. Never the clinical platform.
Cytiva Sefia / Sepax C-Pro	In inventory	Named on the RFP deck. The only platform with published islet proof-of-concept — a single fraction at 75% purity on one human pancreas.
Fresenius Kabi LOVO	In inventory	Named on the RFP deck. Counter-flow washing and concentration; fraction collection is the open question.
Thermo Fisher CTS Rotea	In inventory	Counter-flow centrifugation with programmable fraction output — the closest native analog to collecting fractions across a gradient.
CARR Biosystems UniFuge	Installing Q4 2026	Single-use continuous-flow centrifuge Made is bringing in for its allogeneic MSC platform. Islet purification on it is undemonstrated; it enters as a candidate because it is closed, supported and already operated here — not because it is favored.

WS‑2

The hold-time clock

In-use stability is the window from release to infusion, and every validated hour of it is an hour of shipping reach. The bar below is built only from figures stated in the process description — nothing modeled, nothing assumed.

Validated hold time 48 h

12 h today48 h target96 h stretch

Cold ischemia, <12 h Receipt to static hold, 4–6 h Culture, 24–48 h Release testing, 24–48 h In-use window, release → infusion

Work order 6.0 — what is measured, and when

Hold-time studies from the current 6–12 h through 24, 48, 72 and 96 h in the CIT culture and transport configuration.
At every timepoint: viability (SYTO 13 / ethidium bromide), IEQ recovery and islet volume read together, morphology score, GSIS stimulation index, endotoxin and gram stain. IEQ alone can mask fragmentation and central necrosis.
Pack-out design and six pack-outs for the mock shipments Eledon will execute.

Analytical

Release strategy

The safety panel is proven and in routine GMP use at Made. The islet-specific methods are new and are a development and qualification scope in their own right — work orders 7.0 and 8.0.

Category	Parameter	Made position
Purity / identity	Islet volume, purity, morphology	Develop Automated islet counter methods qualified — five of the twelve RFP parameters on one instrument
Purity / identity	Viability	Adapt SYTO 13 / ethidium bromide transferred and qualified; an automated alternative evaluated in parallel
Strength	Islet yield, IEQ	Develop Dosing-critical; qualified to the 5,000 / 4,500 IEQ/kg basis
Strength	Glucose-stimulated insulin secretion	Develop The potency assay; stimulation-index specification by the time PPQ material is made
Safety	Endotoxin, sterility, mycoplasma	Proven Endosafe, BACT/ALERT and BioFire in routine GMP use; matrix suitability in the islet transport medium
Safety	Gram stain	Proven The release test for transplant, per Eledon; compendial and rapid sterility reported in arrears
Characterization	Enzyme residuals	Develop The one parameter the RFP leaves undefined; the method follows the enzyme decision

Four enzyme options, three 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 decision in work order 2.0 gates 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 & supply

What has to arrive, and who brings it

Four equipment items are missing against the process. Eledon is ordering three of them now; the fourth is selected by the screen. Two supply-side introductions cover the organs and one candidate platform.

Item	Who	Position
BioRep Perfusion System	Eledon procures	Ductal enzyme perfusion. Confirmed 4–6 week lead time. Made issues the user requirement specification, receives and qualifies.
BioRep Ricordi Isolator	Eledon procures	Controlled digestion at 37 °C. Two commissioning digestions on research pancreata before any development run.
BioRep Automated Islet Counter	Eledon procures	Anchors five methods: volume, purity, morphology, IEQ and digestion cell count.
COBE 2991, refurbished	Eledon or Made at cost	Comparability baseline only. Who sources it and how it is serviced after Terumo's sunset is register item 18.
Separation platform	Selected Q2 2027	The binding schedule decision. Sefia / Sepax, LOVO and Rotea are on site; the CARR UniFuge arrives this quarter. Platform assets that serve more than one program are Made's and are not charged to Eledon.
Research pancreata	IIAM via GBC	Whole pancreas within 1–2 days of request against Eledon-set specifications. About thirty organs across Phase 1, passed through at cost. Per-lot enzyme qualification draws one per lot through the campaign.
Clinical pancreata	Eledon	Via organ procurement organizations under Eledon's relationships; Made receives at the dock. East Norriton sits inside the Philadelphia procurement corridor.
Enzymes, gradient and culture media	Made	From the CIT bill of materials; standing qualified lots held in date-controlled readiness. Estimated in the proposal, rebuilt from a bill of materials in work order 1.0.
Cleanrooms, cold chain, cryogenic storage	In place	Princeton and East Norriton infrastructure in routine use. Cadaveric organ receipt is a new workflow on existing infrastructure, qualified in work order 9.0.

The CIT batch record leaves equipment, sterilized items and disposables as institution-specific attachments; work order 2.0 rebuilds the three lists. That is register item 7.

Sites

Develop at Princeton, manufacture at East Norriton

The isolation train is qualified and the team trained at Princeton, where the two must-have workstreams run on research pancreata. Phase 3 clinical supply is proposed for a dedicated Grade B suite at East Norriton. Both are on the 15 September itinerary, and the site decision is Eledon's afterward.

Process development · 2026–2027

Princeton, New Jersey

201 College Road East

Five ISO 7 cleanroom suites, each on its own air handling unit; QC laboratories for environmental, microbial, in-process and release testing.
Process development laboratory where the Eledon-procured train is installed and qualified first (work order 3.0) and WS‑1 and WS‑2 run.
Closed-system platforms in inventory: Sefia / Sepax C-Pro, LOVO, CTS Rotea; the CARR UniFuge arrives this quarter.
In technology transfer toward PPQ on a first in-house allogeneic cell therapy; first FDA inspection expected Q1 2027.
307 College Road East, adjacent, ~55,000–60,000 sq ft in build-out — the campus option for commercial expansion if the program wants it.

GMP manufacture · from Q1 2028

East Norriton, Pennsylvania

2900 Potshop Lane · in commissioning for production from late October 2026

A manufacturing spine of eight Grade B process suites, each with two Grade A biosafety cabinets and its own material / personnel airlocks in from a Grade C supply corridor and out to a Grade C return corridor.
Four further Grade B process rooms and four Grade C flex rooms around a bioreactor hall; 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 on the south side.
Inside the Philadelphia organ procurement corridor — one of the four catchments Eledon named alongside New England, California and Chicago.
Proposed: one dedicated Grade B suite on the spine, with the organ path running dock → inspection → material staging → supply corridor → suite.

East Norriton — ground floor classification plan

Drag to pan, scroll or pinch to zoom, or use the buttons to jump to an area. The plan is the architectural classification plan issued for pricing; commissioning status is reviewed on the day.

Proposed suite & organ path

East Norriton ground floor classification plan

Grade A Grade B Grade C Grade D CNC Source: Precis Engineering / DCI MacIntosh classification plan A-1011, preliminary — not for construction. Suite designation and organ path are Made's proposal for discussion on 15 September, not the qualified route.

Operating model

Receiving organs on no notice

This is the operational problem the program actually poses, and it is a staffing model rather than a scheduling one. A pancreas can arrive at any hour.

Suite reservation. A dedicated Grade B suite held for the program, so a pancreas never waits on a room. Priced monthly in Phase 2 — the reservation buys readiness, the batch fee buys the attempt.
On-call isolation team. A trained, named roster reachable outside shift hours, with call-out and stand-down procedures, priced as a readiness commitment rather than per activation.
Standing materials. Qualified enzyme lots and gradient media held in date-controlled readiness — a batch cannot wait on a reagent order.
Release on the clock. QA and QC coverage matched to the hold time, so a batch is not held by a signature.
Shift coverage. Princeton is moving to a three-shift, seven-day cadence for other reasons; East Norriton is commissioned to the same model.

Stated plainly. Islet isolation is not a capability Made Scientific has previously run. Our cleanroom, cold-chain and safety-testing infrastructure is mature and in routine GMP use, and the team carries commercial cell therapy launch and BLA inspection experience from other organizations — but no one at Made has isolated islets from a human pancreas, and Made has hosted one client audit and no regulatory inspection to date. The proposal is written to make that honest: the first work orders build the capability on the CIT record and research pancreata, and every GMP commitment sits behind a gate Eledon can see. An Eledon-led pre-award audit is invited at no charge.

Timeline

Q4 2026 to the first GMP batch

Sequential from execution of the Phase 1 work order in early October 2026. The two must-have workstreams start immediately on the CIT record and research pancreata; nothing in the first two quarters waits on equipment, the University of Chicago or the platform decision.

Early Oct 2026Phase 1 work order executed — aligned to Eledon's end-of-October CDMO selection

Q2 2027Separation platform selected at the close of WO 4.0 — the binding schedule decision

Q3–Q4 2027WS‑1 and WS‑2 gates

Q1 2028First GMP batch available — one quarter behind the end-2027 start on the RFP deck, shown rather than promised away

What can compress the schedule: a platform that emerges clearly from the screen by the end of Q1 2027, and research pancreata arriving at the IIAM cadence. What can extend it: a platform that needs consumable development, or a 48 h result that forces a return to the culture configuration. The BioRep items, at 4–6 weeks, are not on the critical path.

Proposal

Work orders and fees

Phase 1 — technology transfer, development and readiness — is priced as twelve work orders in five milestones. Phase 2 — Phase 3 clinical supply — is priced per batch against reserved capacity. Every figure is a rough order of magnitude for planning and internal approvals; this is a budgetary estimate, not a quotation and not a binding offer.

PDF

Budgetary Proposal · V01

Letter, alignment, scope and timeline, service fees and work breakdown, Phase 2 scenarios, options, key terms, twelve technical work orders, process and QC appendices, sites. 14 pages, 10 September 2026.

PDF

Response to the RFP Deck · V01

The deck answered slide by slide, Eledon's 1 September responses reproduced verbatim with what each changed, and the register of open items for 15 September. 10 pages.

Phase 1 — service fees and work breakdown

Phase 2 — Phase 3 clinical supply, per batch against reserved capacity

Contracted on passage of the WS‑1 and WS‑2 gates under a Capacity Reservation Agreement. Three volume scenarios because the batch count is the largest open commercial variable: 24 is one dose per Phase 3 patient; 50 and 75 bracket the RFP deck.

Options, not in either total

Two gates At the close of WO 4.0 with the platform selected, and at the close of WO 6.0 with 48 h demonstrated. Eledon may stop at either with no charge for work orders not initiated and the deposit refunded less work performed.

Equipment Eledon-procured assets remain Eledon's, installed and qualified by Made under change control; calibration and maintenance coordinated by Eledon under the Quality Agreement. Shared platform assets remain Made's and are not charged.

Batch failure Written on cause, as Eledon put it. Made-attributable attempts are repeated at no service fee, materials at cost. Organ-attributable attempts carry a reduced fee — proposed at half the batch price when terminated before purification, full thereafter, less release testing not performed.

Intellectual property Made takes no IP in Eledon's program. The platform process description, the hold-time data, the qualified islet methods and the comparability data remain Eledon's, including if manufacture later moves.

Set against the 31 August framework's ranges — $12.9M to $27.5M through the BLA — the proposal lands in the lower half: Eledon's decision to procure the isolation train removed $0.5M to $1.0M of capital, and a batch is priced at a point inside the earlier $125K–$200K band. Service fees are firm on signature except WO 5.0 and WO 11.0, confirmed when the platform is known. Pancreata, materials and outsourced services are estimates rebuilt from a bill of materials in WO 1.0 and billed at cost plus 15%.

Assumptions

What these figures rest on

Assumed

One donor pancreas processed to one patient dose, released fresh at 2–8 °C; a batch is one manufacturing attempt.
Eledon procures the BioRep train and the comparability COBE; Made specifies, receives, installs and qualifies. Capital is out of the totals.
Research pancreata via IIAM, about thirty across Phase 1, at cost plus 15%. Clinical procurement, OPO contracting and donor screening are Eledon's.
The CIT record is the process basis; the University of Chicago delta is applied when it lands.
Phase 2 assumes a 24-month campaign from Q1 2028 and no control arm.
Gram stain at release; compendial and rapid sterility reported in arrears, subject to CBER agreement.

Excluded

Tegoprubart manufacture, supply or handling.
Commercial supply from 2030 — a separate agreement, discussed late 2027 or early 2028 at Eledon's request.
Stem-cell-derived or iPSC islet programs.
WS‑3 cryopreservation, the University of Chicago person-in-plant and the commercial facility design package — options.
Clinical site logistics beyond the qualified pack-out.
Regulatory filing fees and Eledon-side CMC authoring.

Register

Open items for 15 September

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15 September

Site visit — Princeton and East Norriton

A single day across both sites, 09:30–16:00, structured so the register above gets closed rather than reopened. Select a session to see the items it is meant to settle.

Attending

Made Scientific — Joseph Sinclair (Commercial), Chathuranga De Silva, David Smith (Development, inbound technology transfer), Irving Ford (Quality and Compliance), Michelle Ng (Program Management), Jill Gliem, Syed Husain, Lee McDonald (Regulatory).

Eledon Pharmaceuticals — Carlos Candido (Vice President, Cell Therapy Operations), Laura Folk (Head of GMP Quality).

Eledon reviews the proposal and the response before the visit, so 15 September closes items rather than introducing them. Questions to Joe Sinclair at any time.
Made issues the equipment user requirement specifications for the BioRep train, so the orders Eledon is placing arrive to a specification Made will qualify.
Eledon confirms the CARR UniFuge in the screen and whether a technical session with CARR Biosystems is wanted before the screen is designed.
Research pancreas supply confirmed with IIAM against Eledon-set specifications, so the platform screen can start on execution.
Phase 1 work order executed early October, aligned to Eledon's end-of-October CDMO selection and term sheet; the Quality Agreement opened in parallel.