📚 Part of the TILA-278 Regulatory Dossier — Reader's Guide. This article shows the live document; edits to the source appear here automatically.

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EU MAA — Application Form (eAF) & Cover Letter (TILA-278)

Field	Value
Document ID	M1-eAF
Version	1.0
Compound	TILA-278 (anti-TL1A antagonist / IL-22R agonist bispecific)
Standard	EU EMA
Confidentiality	Confidential

Region-specific administrative document for the TILA-278 marketing application.

Change History

Version	Date	Author	Summary
1.0	2026-07-08	Regulatory Affairs	Initial issue

Module 1.0 — Cover Letter

Virtual Biopharma Inc. Regulatory Affairs — European Operations 12 Grand Canal Quay, Dublin 2, D02 XY45, Ireland

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To	European Medicines Agency — Human Medicines Division
	Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
Date	09 July 2026
EMA product number	EMEA/H/C/006278
Procedure	Centralised Procedure — New Marketing Authorisation Application
Our reference	VBP/RA/EU/TILA278/MAA-001

Subject: Submission of a new Marketing Authorisation Application for Enterluma (TILA-278, proposed INN tilrivamig) 300 mg solution for injection in pre-filled syringe and pre-filled pen, under Article 8(3) of Directive 2001/83/EC.

Dear Sir or Madam,

On behalf of Virtual Biopharma Inc., acting through its EEA-established affiliate Virtual Biopharma Ireland Ltd (the applicant and proposed Marketing Authorisation Holder), we hereby submit an initial Marketing Authorisation Application (MAA) for the above medicinal product through the centralised procedure. The application is submitted in electronic Common Technical Document (eCTD) format and is provided in full in Modules 1 to 5.

Basis for the centralised procedure. TILA-278 is a recombinant humanised IgG1 bispecific monoclonal antibody produced by recombinant DNA technology in a Chinese Hamster Ovary (CHO) cell line. The product therefore falls within the mandatory scope of the centralised procedure under Article 3(1) of Regulation (EC) No 726/2004, point 1 of the Annex (medicinal products developed by means of recombinant DNA technology).

Legal basis. The application is a complete and independent (full) application under Article 8(3) of Directive 2001/83/EC, supported by the applicant's own quality, non-clinical and clinical data. TILA-278 contains a new active substance not previously authorised in the Union; the new active substance claim is documented in Module 1.5.2.

Therapeutic indication (proposed). Treatment of adults with moderately to severely active ulcerative colitis who have had an inadequate response with, lost response to, or were intolerant to conventional therapy or a biologic agent. The proposed indication and posology are set out in the draft SmPC (Module 1.3.1) and are supported by the pivotal Phase 2b induction study TILA278-201.

Pre-submission history. Eligibility to the centralised procedure was confirmed by the CHMP on 12 March 2026. A pre-submission meeting with the (Co-)Rapporteur teams and the EMA Product Lead was held on 27 May 2026. Scientific advice on the clinical development programme and on reliance on a single pivotal induction study was received under procedure EMEA/H/SA/5xxx/1/2024/III. The applicant has been granted access to the PRIME scheme for this product (EMEA/H/PR/xxxx). This application is not submitted under an accelerated assessment request; a conditional marketing authorisation is not requested at this time.

Paediatric requirements. An agreed Paediatric Investigation Plan with a deferral for the paediatric ulcerative colitis population is in place (PDCO decision EMEA-00xxxx-PIP01-24); the compliance statement is provided in Module 1.5.1.

Orphan status. The product does not hold an orphan designation for this indication.

Environmental risk assessment. In accordance with the CHMP guideline EMEA/CHMP/SWP/4447/00, a full ERA is not required: the active substance is a protein (monoclonal antibody) that is expected to be metabolised to endogenous amino acids and to pose a negligible risk to the environment. The justification is provided in Module 1.6.

Pharmacovigilance. A summary of the applicant's pharmacovigilance system is provided in Module 1.8.1, with the Pharmacovigilance System Master File (PSMF) reference number PSMF-VBP-2019-0004. The EU Risk Management Plan (EU-RMP version 1.0, dated 30 June 2026) is provided in Module 1.8.2.

Fee. The applicable fee under the EMA fee regulation has been arranged; the fee form is enclosed. SME status is not claimed.

Specific requests to the Agency.

• Review of the proposed (invented) name Enterluma by the Name Review Group.
• Confirmation of new active substance status.
• Appointment of the QRD template review for the enclosed Product Information.

We confirm that the information submitted is, to the best of our knowledge, accurate and complete, and that the dossier complies with the Notice to Applicants and applicable ICH guidelines. The undersigned is authorised to act on behalf of the applicant.

Yours faithfully,

Dr Helena Vasquez Vice-President, Global Regulatory Affairs — EU Qualified Signatory Virtual Biopharma Inc. Tel: +353 1 555 0100 · E-mail: [email protected]

Enclosures: eCTD sequence 0000 (Modules 1–5); Fee form; Letters of authorisation; Proof of establishment in the EEA; GMP documentation.

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Module 1.2 — Application Form (eAF)

Executed electronic Application Form (EU Human eAF) for a Marketing Authorisation for a medicinal product for human use — Centralised Procedure.

1. Type of Application

1.1 This application concerns:

Field	Entry
Procedure	Centralised Procedure
Scope	Mandatory — Article 3(1) of Regulation (EC) No 726/2004, Annex point 1 (recombinant DNA technology)
Nature of application	New Marketing Authorisation Application
Number of the present application	One (single) marketing authorisation

1.2 The undersigned submits an application for the medicinal product identified in Section 2, on the basis of:

Legal basis	Selected	Note
Article 8(3) of Dir. 2001/83/EC — full/complete application	☒	Applicant's own complete data (quality, non-clinical, clinical)
Article 10(1) — generic	☐
Article 10(3) — hybrid	☐
Article 10(4) — similar biological (biosimilar)	☐
Article 10a — well-established use	☐
Article 10b — fixed combination	☐
Article 10c — informed consent	☐

1.3 The application is submitted in accordance with the following:

Feature	Applicable	Reference
New active substance	Yes	Module 1.5.2 (NAS claim)
Accelerated assessment (Art. 14(9) Reg. 726/2004)	No	—
Conditional marketing authorisation (Reg. 507/2006)	No	—
Marketing authorisation under exceptional circumstances	No	—
PRIME (priority medicines)	Yes	EMEA/H/PR/xxxx
Orphan medicinal product	No	—
Advanced therapy medicinal product	No	—
Global marketing authorisation — first product of the GMA	Yes	Art. 6(1) Dir. 2001/83/EC

2. Marketing Authorisation Application Particulars

2.1 Name and ATC code of the medicinal product

Item	Entry
Proposed (invented) name	Enterluma
Active substance — common name (INN)	Proposed INN tilrivamig; INN application with WHO ongoing
Company/product internal code	TILA-278
Pharmacotherapeutic group	Immunosuppressants, interleukin inhibitors / selective immunomodulators
ATC code	2000 L04AC (to be confirmed by the WHO Collaborating Centre)

2.1.2 Strength(s), pharmaceutical form, route of administration, container and pack sizes:

Strength	Pharmaceutical form	Route	Container / closure	Pack sizes
300 mg	Solution for injection	Subcutaneous use	Single-use, glass Type I pre-filled syringe (2 mL fill; 300 mg) with fixed needle and passive needle-guard	1, 2
300 mg	Solution for injection	Subcutaneous use	Single-use pre-filled pen (autoinjector; 2 mL fill; 300 mg)	1, 2

Each single-use pre-filled syringe or pre-filled pen delivers 2.0 mL at a protein concentration of 150 mg/mL, corresponding to 300 mg of tilrivamig per unit. The induction regimen is administered as one or two units per dose; the posology for the 12-week induction period is defined in the SmPC (Module 1.3.1).

2.2 Legal status / proposed classification for supply

Field	Entry
Proposed classification	Medicinal product subject to medical prescription (Art. 71 Dir. 2001/83/EC)
Restricted medical prescription	Restricted to use by, or under the supervision of, a physician experienced in the diagnosis and treatment of ulcerative colitis / inflammatory bowel disease
Self-administration	Permitted after appropriate training (SC pre-filled syringe / pen)

2.3 Marketing Authorisation Holder, contact persons and Qualified Person for Pharmacovigilance

2.3.1 Proposed Marketing Authorisation Holder (established in the EEA):

Field	Entry
Name	Virtual Biopharma Ireland Ltd (EEA-established affiliate of Virtual Biopharma Inc.)
Address	12 Grand Canal Quay, Dublin 2, D02 XY45, Ireland
Country	Ireland
Telephone / E-mail	+353 1 555 0100 / [email protected]

2.3.2 Person authorised for communication with the Agency during the procedure:

Field	Entry
Name	Dr Helena Vasquez
Function	VP, Global Regulatory Affairs — EU
Contact	+353 1 555 0110 / [email protected]

2.3.3 Person/company authorised for communication between the MAH and authorities after authorisation: As per 2.3.2 (Regulatory Affairs — EU).

2.3.4 Qualified Person responsible for Pharmacovigilance (QPPV):

Field	Entry
Name	Dr Anders Møller
Residence and operation	Resident and operating in the European Union (Ireland)
24-hour contact	+353 1 555 0199 (24/7) / [email protected]
PSMF location	12 Grand Canal Quay, Dublin 2, Ireland
PSMF reference number	PSMF-VBP-2019-0004

2.3.5 Scientific service in charge of information about the medicinal product (Art. 98 Dir. 2001/83/EC): Medical Information — Virtual Biopharma Ireland Ltd, Dublin.

2.4 Manufacturers

2.4.1 Manufacturer(s) responsible for batch release in the EEA:

Name	Address	Manufacturing authorisation / GMP
Virtual Biopharma Manufacturing GmbH	Industriestrasse 45, 68305 Mannheim, Germany	MIA DE_BW_01_MIA_2020_0123; GMP certificate DE/GMP/2024/0456

2.4.2 Official batch release (OCABR): Not applicable — a monoclonal antibody is not subject to Official Control Authority Batch Release.

2.4.3 Manufacturer(s) of the medicinal product / site(s) of manufacture (drug product — formulation, fill/finish, primary and secondary packaging):

Name	Site / operations	GMP evidence
Virtual Biopharma Manufacturing GmbH	Mannheim, Germany — DP compounding, aseptic fill of pre-filled syringes, assembly of pre-filled pen, packaging	GMP certificate DE/GMP/2024/0456
NordAseptic Fill-Finish A/S (contract)	Copenhagen, Denmark — secondary packaging and labelling	GMP certificate DK/GMP/2023/0789

2.4.4 Manufacturer(s) of the active substance (drug substance):

Name	Site / operations	GMP / evidence
Virtual Biopharma Biologics Inc.	Cambridge, MA, USA — CHO cell culture, harvest, Protein A capture, polishing chromatography, viral clearance, UF/DF, DS filling	FDA-registered; GMP for the active substance confirmed per Module 3.2.S; QP declaration in Module 1.5.5

2.4.5 Contract quality-control site(s):

Name	Testing
Virtual Biopharma Manufacturing GmbH (Mannheim, DE)	Release and stability testing of DS and DP, including both bioassays (anti-TL1A neutralisation; IL-22R agonism)
EuroBioAnalytics S.A. (Lyon, FR) — contract	Compendial microbiological testing, container-closure integrity

2.4.6 Flow-chart of the manufacturing/importation network: A narrative and diagram of the DS→DP→QC-release→EEA batch-release network are provided in Module 3.2.A and Module 1.5.5 (QP declaration on GMP for active substance manufacture outside the EEA, per Art. 46(f) Dir. 2001/83/EC).

2.5 Qualitative and quantitative composition

2.5.1 Composition — active substance and excipients (per pre-filled syringe / pen, delivering 2.0 mL / 300 mg):

Component	Function	Quantity
Tilrivamig (TILA-278), recombinant humanised IgG1 bispecific mAb (CHO)	Active substance	300 mg
L-Histidine / L-histidine hydrochloride monohydrate	Buffer	q.s. pH 5.8
Sucrose	Stabiliser / tonicity	160 mg
Polysorbate 80	Surfactant	0.8 mg
Water for injections	Solvent	q.s. to 2.0 mL

No overage is applied. The finished product is a preservative-free, single-use presentation at a nominal protein concentration of 150 mg/mL. Full quantitative composition, reference to Ph. Eur. monographs and the container-closure system are described in Module 3.2.P.1.

2.5.2 Materials of animal or human origin (TSE): No materials of human origin are used. The active substance is expressed in a rodent (CHO) cell line; the manufacturing process does not use ruminant-derived materials of TSE concern. A statement of compliance with the Note for Guidance EMEA/410/01 (TSE) and Ph. Eur. 5.2.8 is provided in Module 3.2.A.2.

2.5.3 Genetically modified organisms (GMO): The finished product does not contain and does not consist of GMOs within the meaning of Directive 2001/18/EC. The CHO production cell line is genetically engineered but is fully contained during manufacture and is not present in the product.

3. Scientific Advice, Studies and Additional Data

Item	Entry
Scientific advice received (EMA)	Yes — EMEA/H/SA/5xxx/1/2024/III (single pivotal induction study; immunogenicity strategy; CMC comparability)
Pivotal clinical study	TILA278-201 — Phase 2b, randomised, double-blind, placebo-controlled, parallel-group, 12-week induction study in moderately-to-severely active UC (1700 screened; 900 randomised 1:1:1 to TILA-278 High / TILA-278 Low / Placebo, 299/300/301)
Primary endpoint met	Yes — clinical remission (modified Mayo ≤ 2, no subscore > 1) at Week 12
Clinical overview / summaries	Module 2.5 / 2.7
Environmental risk assessment	Module 1.6 — full ERA exempt (protein active substance)

4. Product Information (Module 1.3)

The following are enclosed in the current QRD template, in English (the applicant will provide translations at the linguistic review stage):

• 1.3.1 Summary of Product Characteristics (SmPC)
• 1.3.2 Labelling (outer and immediate packaging — pre-filled syringe and pre-filled pen)
• 1.3.3 Package Leaflet
• 1.3.4 Mock-ups and specimens
• 1.3.6 Braille statement and user-consultation (readability) report

5. Annexed and Supporting Documents (Module 1)

Annex	Document	Location
A	Proof of establishment of the applicant in the EEA	1.2
B	Letter(s) of authorisation for communication on behalf of the applicant	1.2
C	Manufacturing authorisation(s) and GMP certificate(s) for DP and batch-release sites	1.2 / EudraGMDP references
D	QP declaration on GMP compliance of the active substance manufacturer (Art. 46(f))	1.5.5
E	New active substance claim and supporting justification	1.5.2
F	Environmental risk assessment justification	1.6
G	Summary of the pharmacovigilance system (with PSMF number)	1.8.1
H	EU Risk Management Plan (EU-RMP)	1.8.2
I	PIP compliance statement / PDCO decision	1.5.1
J	Letters of access / declarations (invented name, PRIME)	1.5

6. Risk Management Plan — Reference and Safety Specification Summary

The EU-RMP (version 1.0, 30 June 2026; Module 1.8.2) is aligned with the safety database from study TILA278-201 (TEAEs in 109 / 131 / 130 subjects for High / Low / Placebo; SAEs 3 / 0 / 4; deaths 2 / 0 / 1, all assessed as unrelated to study drug; discontinuations 17 / 17 / 29, with placebo discontinuations predominantly for lack of efficacy). The safety specification is summarised below.

RMP element	Content
Important identified risk	Injection-site reactions (the principal drug-attributable finding; higher with active subcutaneous treatment than placebo)
Important potential risks	Serious and opportunistic infections (immunomodulation); hypersensitivity and immunogenicity-related reactions; malignancy (theoretical class consideration for immunomodulators)
Missing information	Use in pregnancy and lactation; long-term safety beyond the 12-week induction period; use in the elderly; long-term immunogenicity impact on efficacy/safety
Routine pharmacovigilance	Standard AE collection; targeted follow-up questionnaires for infections, hypersensitivity and pregnancy; PSUR/PBRER cycle
Additional pharmacovigilance	prospective UC disease/drug registry; ongoing Phase 3 induction–maintenance and long-term extension studies
Routine risk minimisation	SmPC Sections 4.2, 4.3, 4.4, 4.6, 4.8; Package Leaflet; prescription-only, restricted prescribing
Additional risk minimisation	patient reminder/alert card for signs of infection and hypersensitivity

Consistency note (efficacy supporting the benefit–risk in the RMP): LS-mean change in modified Mayo at Week 12 was −3.36 (High), −2.76 (Low) and −1.00 (Placebo); difference versus placebo −2.36 (95% CI −2.49, −2.23; p<0.0001) for High and −1.77 (95% CI −1.90, −1.64; p<0.0001) for Low. Week-12 clinical remission was dose-ordered at 37.3% (106/284), 16.2% (46/283) and 0.7% (2/273) for High, Low and Placebo, respectively.

7. Declaration and Signature of the Applicant

The undersigned confirms that:

• the particulars given in this application are correct and complete to the best of their knowledge;
• the dossier is submitted in accordance with Regulation (EC) No 726/2004, Directive 2001/83/EC, the Notice to Applicants and applicable ICH guidelines (including ICH M4 CTD organisation, ICH S6(R1) for the non-clinical evaluation of the biotechnology-derived active substance, and the ICH E14/S7B waiver rationale for the QT assessment of a monoclonal antibody);
• the manufacturing and control operations comply with the principles of Good Manufacturing Practice; and
• the applicant undertakes to fulfil the pharmacovigilance obligations set out in Title IX of Directive 2001/83/EC and Regulation (EC) No 726/2004.

Field	Entry
Name	Dr Helena Vasquez
Function	VP, Global Regulatory Affairs — EU (authorised signatory)
On behalf of	Virtual Biopharma Ireland Ltd (affiliate of Virtual Biopharma Inc.)
Place / Date	Dublin, 09 July 2026
Signature	(signed electronically)