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

---

US BLA — Form FDA 356h, Cover Letter & Certifications (TILA-278)

Field	Value
Document ID	M1-356h
Version	1.0
Compound	TILA-278 (anti-TL1A antagonist / IL-22R agonist bispecific)
Standard	US FDA (BLA)
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 1.1 — Forms

1.1.1 Form FDA 356h — Application to Market a New or Abbreviated New Drug, Biologic, or an Antibiotic Drug for Human Use

Executed copy. The original bearing the responsible official's signature is retained by the applicant and provided in the signed PDF leaf of this submission.

APPLICATION TO MARKET A NEW OR ABBREVIATED NEW DRUG OR BIOLOGIC FOR HUMAN USE (Form FDA 356h)

Field	Entry
1. Name of applicant	Virtual Biopharma Inc.
Telephone / email	+1-617-555-0142 / [email protected]
2. Applicant address	100 Innovation Way, Cambridge, MA 02142, USA
Authorized U.S. agent (if applicable)	Not applicable — applicant is a domestic entity
3. Product description — Proprietary (trade) name	To be assigned; a proposed proprietary name has been submitted for review under separate correspondence (proprietary-name review request)
Established / proper name	tilazumig (proposed nonproprietary name, consistent with the WHO "-mig" stem for multispecific immunoglobulins); development code TILA-278
Molecule class	Recombinant humanized IgG1 bispecific monoclonal antibody (anti–TL1A [TNFSF15] antagonist arm; IL-22 receptor agonist arm)
Dosage form	Sterile solution for injection
Strength / content	150 mg/mL; single-use prefilled syringe and single-use autoinjector each delivering 150 mg per 1.0 mL
Route of administration	Subcutaneous (SC)
4. Application / product number	Original application — number to be assigned by CDER upon receipt BLA 76XXXX
5. Type of application	☒ This is a NEW application. Submitted as an original Biologics License Application under section 351(a) of the Public Health Service Act (42 U.S.C. 262(a)) and 21 CFR 601.2. Not a 351(k) biosimilar application.
☐ Amendment / ☐ Resubmission / ☐ Supplement	Not applicable
6. If a supplement, identify type	Not applicable
7. Proposed indication(s) for use	Treatment of adults with moderately to severely active ulcerative colitis (UC). Efficacy and safety are established for induction of clinical remission in the pivotal study (Protocol TILA278-201); proposed labeling and the clinical program are described in Modules 2 and 5.
8. Related submissions (cross-references)	IND 168,4XX (TILA-278, active); proposed proprietary-name correspondence; initial pediatric study plan (iPSP) agreed under PREA; drug master files referenced in Section 1.4.1 (letters of authorization enclosed)

Establishments associated with the manufacture of the product (full addresses, registration numbers, and functions provided in Module 1.3.1 / 3.2.A):

Function	Establishment	Registration (FEI/DUNS)
Drug substance manufacture (CHO cell culture, protein-A + polishing chromatography, viral clearance, purification)	Virtual Biopharma Biologics Operations, Devens, MA, USA	FEI 300XXXXXXX
Drug product manufacture / fill-finish (aseptic fill, prefilled syringe and autoinjector assembly, labeling, packaging)	Contract fill-finish facility, Dublin, Ireland	FEI 300XXXXXXX
Stability, release, and quality-control testing	Virtual Biopharma QC, Devens, MA, USA; and contract QC laboratory	FEI 300XXXXXXX

All named establishments are registered and, to the applicant's knowledge, in compliance with current good manufacturing practice (cGMP) under 21 CFR Parts 210, 211, and the applicable provisions of Parts 600–680. A statement of readiness for pre-license inspection is included at Section 1.3.1.

The application contains the following items (organized in eCTD Modules 1–5 per the ICH Common Technical Document and the FDA eCTD Comprehensive Table of Contents):

#	Item	Included	Location
1	Index (comprehensive table of contents)	☒	eCTD backbone (index.xml)
2	Labeling (proposed prescribing information, carton/container labels, Instructions for Use)	☒	1.14
3	Summary (Module 2 CTD summaries)	☒	Module 2
4	Chemistry, manufacturing, and controls (CMC)	☒	Module 3
5	Samples	☒	Provided on request
6	Methods validation package	☒	Module 3.2.S / 3.2.P
7	Nonclinical pharmacology and toxicology	☒	Module 4
8	Human pharmacokinetics and bioavailability / clinical pharmacology	☒	Module 5.3.1 / 5.3.3
9	Clinical microbiology	☐ N/A	Not applicable (monoclonal antibody)
10	Clinical data (including pivotal Study TILA278-201)	☒	Module 5
11	Safety update report	☒	Submitted as a 120-day safety update during the review cycle
12	Statistical analyses	☒	Module 5.3.5
13	Case report tabulations / datasets (SDTM / ADaM)	☒	Module 5.3.7
14	Case report forms (deaths, discontinuations, SAEs)	☒	Module 5.3.7
15	Patent information (FD&C Act § 505(b)(1))	☐ N/A	1.3.5 (does not apply to a 351(a) BLA)
16	Patent certification	☐ N/A	1.3.5
17	Establishment description	☒	3.2.A.1
18	Debarment certification	☒	1.3.3
19	Field copy certification	☐ N/A	1.3.2 (not applicable to an all-electronic submission)
20	User fee cover sheet (Form FDA 3397)	☒	1.1.3
21	Financial certification and disclosure (Forms FDA 3454 / 3455)	☒	1.3.4
22	Certification of compliance, ClinicalTrials.gov (Form FDA 3674)	☒	1.1.4
23	Pediatric use information (PREA / iPSP)	☒	1.9

CERTIFICATION

I certify that all statements made in this application are true and correct. As the responsible official of the applicant, I agree to comply with all applicable laws and regulations that apply to approved applications, including but not limited to the following:

1. Good manufacturing practice regulations in 21 CFR Parts 210, 211, and applicable provisions of 600–680.
2. Biological product standards in 21 CFR Parts 600–680.
3. Labeling regulations in 21 CFR Parts 201 and 610.
4. Prescription-drug advertising regulations in 21 CFR Part 202.
5. Regulations on making changes in the application under 21 CFR 601.12.
6. Regulations on reports under 21 CFR 600.80, 600.81, and 601.28.
7. Local, state, and federal environmental impact laws.

If this application is approved, I agree to update it and submit reports as required by law and FDA regulation.

I understand that a willfully false statement is a criminal offense under 18 U.S.C. 1001.

Signature block	Entry
Signature of responsible official or agent	(executed — signature applied)
Typed name and title	Jane A. Doe, PhD, RAC — Chief Regulatory Officer & Head of Global Regulatory Affairs
Address	Virtual Biopharma Inc., 100 Innovation Way, Cambridge, MA 02142
Telephone / email	+1-617-555-0142 / [email protected]
Date	09 July 2026

1.1.3 User Fee Cover Sheet and Certification (Form FDA 3397)

Submitted pursuant to the Prescription Drug User Fee Act (PDUFA, as reauthorized), section 736 of the FD&C Act.

Form FDA 3397 — Prescription Drug User Fee Cover Sheet

Field	Entry
Company / applicant	Virtual Biopharma Inc.
Product name	TILA-278 (development code; proposed nonproprietary name tilazumig)
Application type	Original BLA under § 351(a) PHS Act
Does the application contain clinical data (other than bioavailability/bioequivalence) supporting safety and effectiveness?	☒ Yes — the application relies on clinical data (pivotal Study TILA278-201) and is therefore subject to the full application fee
Fee category	Human drug application requiring clinical data
PDUFA fiscal year	FY2026
Application fee amount due	$4,310,002 (full application fee, FY2026 fee schedule)
Fee payment status	Paid
Payment identification number (PIN) / User Fee ID	UF-2026-0XXXX
Cover-sheet (PDUFA) tracking number	PN-2026-XXXXXX
Small-business / other fee waiver or reduction claimed	☐ No — applicant does not qualify for and does not claim a small-business waiver or reduction
Organization is current on all previously assessed program fees	☒ Yes

User Fee Certification. Virtual Biopharma Inc. certifies that the correct PDUFA application fee for a human drug/biologic application requiring clinical data has been determined for FY2026 and paid in full prior to or concurrent with submission of this application, that the payment identification number above corresponds to that payment, and that the applicant is not in arrears on any prescription-drug program fees previously assessed. The applicant understands, pursuant to section 736(a) of the FD&C Act and the Agency's user-fee guidance, that FDA will not file this application until the associated user fee is paid, and the applicant affirms that payment has been made.

Signed: (executed) Robert K. Lee, MBA — Chief Financial Officer, Virtual Biopharma Inc. — 09 July 2026.

1.1.4 Certification of Compliance with ClinicalTrials.gov Requirements (Form FDA 3674)

Submitted pursuant to 42 U.S.C. 282(j)(5)(B) (section 402(j) of the Public Health Service Act).

The applicant certifies that the applicable requirements of 42 U.S.C. 282(j) regarding registration and results information for applicable clinical trials have been met for the clinical trial referenced in this application. The pivotal induction study, Protocol TILA278-201, is registered in the ClinicalTrials.gov data bank under National Clinical Trial identifier NCT0XXXXXXX, and results information will be submitted within the timeframe required by 42 U.S.C. 282(j). The executed Form FDA 3674 is provided as a signed leaf of this submission.

Signed: (executed) Jane A. Doe, PhD, RAC — Chief Regulatory Officer, Virtual Biopharma Inc. — 09 July 2026.

---

Module 1.2 — Cover Letter

VIRTUAL BIOPHARMA INC. 100 Innovation Way, Cambridge, MA 02142, USA

09 July 2026

Director, Division of Gastroenterology Office of Immunology and Inflammation, Office of New Drugs Center for Drug Evaluation and Research U.S. Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993-0002

RE: Original Biologics License Application (BLA) submitted under section 351(a) of the PHS Act — TILA-278 (development code; proposed nonproprietary name tilazumig) injection, 150 mg/mL, for subcutaneous administrationProposed indication: treatment of adults with moderately to severely active ulcerative colitisIND 168,4XX; eCTD sequence 0000 (original application)

Dear Director:

On behalf of Virtual Biopharma Inc. (Virtual Biopharma), and in accordance with section 351(a) of the Public Health Service Act (42 U.S.C. 262(a)) and 21 CFR 601.2, we are pleased to submit this original Biologics License Application (BLA) for TILA-278, a recombinant humanized IgG1 bispecific monoclonal antibody for subcutaneous administration, for the treatment of adults with moderately to severely active ulcerative colitis (UC). As a therapeutic monoclonal antibody, TILA-278 is a biological product for which CDER has review responsibility under section 351(a) of the PHS Act.

Product and rationale. TILA-278 is a single bispecific antibody engineered to act through two complementary, disease-relevant mechanisms in UC. One arm antagonizes TL1A (TNFSF15), dampening TH1/TH17-driven mucosal inflammation and the profibrotic signaling that contributes to intestinal fibrosis; the second arm acts as an agonist at the IL-22 receptor, driving intestinal epithelial regeneration, antimicrobial peptide and mucin production, and mucosal-barrier repair. This combined anti-inflammatory and mucosal-healing mechanism is intended to address both the inflammatory and the epithelial-repair dimensions of UC within one molecule. TILA-278 is presented as a sterile solution in a single-use prefilled syringe and a single-use autoinjector.

Basis for licensure. The efficacy and safety of TILA-278 are supported by the pivotal Phase 2b study TILA278-201, a randomized, double-blind, placebo-controlled, parallel-group 12-week induction study in moderate-to-severe UC. Of 1,700 subjects screened, 900 were randomized 1:1:1 to TILA-278 High (n=299), TILA-278 Low (n=300), or placebo (n=301), stratified by baseline modified Mayo severity and prior biologic exposure, with visits at Weeks 0, 2, 4, 8, and 12. The primary endpoint — clinical remission (modified Mayo score ≤ 2 with no individual subscore > 1) at Week 12 — was met with a clear dose-ordered effect: clinical remission was achieved by 37.3% (106/284) of High-dose subjects, 16.2% (46/283) of Low-dose subjects, and 0.7% (2/273) of placebo subjects. The LS-mean change from baseline in modified Mayo score at Week 12 (ANCOVA, full analysis set) was −3.36 (High), −2.76 (Low), and −1.00 (placebo); the difference versus placebo was −2.36 (95% CI −2.49, −2.23; p<0.0001) for the High dose and −1.77 (95% CI −1.90, −1.64; p<0.0001) for the Low dose. TILA-278 was well tolerated with no dose-dependent safety signal; injection-site reactions were the principal drug-attributable finding, while worsening UC and treatment discontinuations were more frequent on placebo (driven by lack of efficacy). The proposed indication is scoped to induction of clinical remission; maintenance of remission and longer-term safety are being characterized in the ongoing study TILA278-301, and those data will be submitted by supplement as they become available. A full account of efficacy, safety, and benefit–risk is provided in Modules 2.5, 2.7, and 5.

Application format and content. This application is submitted in electronic Common Technical Document (eCTD) format and is organized in Modules 1–5 in accordance with the ICH M4 CTD guidance and the FDA eCTD technical specifications. The submission includes the completed Form FDA 356h, this cover letter, the administrative and certification items enumerated below, the CMC package (Module 3) for the CHO-derived drug substance and the prefilled-syringe/autoinjector drug product, the nonclinical package (Module 4) conducted consistent with ICH S6(R1), the clinical pharmacology and clinical data (Module 5), and the proposed prescribing information and Instructions for Use (Module 1.14).

Regulatory background and requests. We respectfully note the following:

• Meetings. The design of Study TILA278-201, the proposed CMC control strategy, and the overall content of this BLA reflect advice received at the pre-IND meeting, the End-of-Phase-2 meeting, the pre-BLA meeting, and associated written responses (meeting reference numbers and minutes provided in Section 1.6.3).
• Expedited programs and review. Breakthrough Therapy designation is in effect for this indication (designation reference). Consistent with that designation, we request Priority Review of this application and the review benefits associated with Breakthrough Therapy designation.
• User fee. The Form FDA 3397 user-fee cover sheet and the associated User Fee Certification are provided in Section 1.1.3; the applicable PDUFA application fee has been paid.
• ClinicalTrials.gov. The certification of compliance under 42 U.S.C. 282(j) (Form FDA 3674) is provided in Section 1.1.4; Study TILA278-201 is registered under NCT0XXXXXXX.
• Pediatric assessment. An initial pediatric study plan has been agreed under the Pediatric Research Equity Act (PREA); see Section 1.9.
• Environmental. A claim of categorical exclusion under 21 CFR 25.31 is provided; no extraordinary circumstances are known, and an Environmental Assessment is therefore not required.
• Proprietary name. A proposed proprietary name has been submitted for review under separate correspondence.
• Establishment inspections. The manufacturing establishments named in Form FDA 356h are ready for pre-license inspection; a facility-readiness statement is provided in Section 1.3.1.

Certifications and administrative documents enclosed. This application includes the following, each addressed in the sections that follow:

Document	Form	Location
User Fee Cover Sheet and Certification	FDA 3397	1.1.3
Certification of Compliance, ClinicalTrials.gov	FDA 3674	1.1.4
Debarment Certification (FD&C Act § 306(k)(1))	Narrative	1.3.3
Financial Certification and Disclosure	FDA 3454 / FDA 3455	1.3.4
Patent Information and Certification Statement	Narrative	1.3.5

Point of contact. All correspondence regarding this application should be directed to the undersigned or to the regulatory project lead identified in Section 1.3.1.

We believe this application demonstrates the safety, purity, and potency of TILA-278 and supports its licensure for the treatment of moderately to severely active ulcerative colitis. We look forward to the Agency's filing determination and to working with the review team throughout the review. Please contact us with any questions or requests for information.

Respectfully submitted,

(executed — signature applied) Jane A. Doe, PhD, RAC Chief Regulatory Officer & Head of Global Regulatory Affairs Virtual Biopharma Inc. +1-617-555-0142 / [email protected]

Enclosures: Form FDA 356h; Form FDA 3397; Form FDA 3674; Forms FDA 3454/3455; Debarment Certification; Patent Information and Certification Statement; claim of categorical exclusion (21 CFR 25.31); eCTD Modules 1–5.

---

Module 1.3 — Administrative Information

1.3.3 Debarment Certification

Submitted pursuant to section 306(k)(1) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 335a(k)(1)).

DEBARMENT CERTIFICATION

The undersigned, as an authorized official of Virtual Biopharma Inc. (the applicant), submits this certification in connection with the original Biologics License Application for TILA-278 (development code; proposed nonproprietary name tilazumig), submitted under section 351(a) of the Public Health Service Act.

Pursuant to section 306(k)(1) of the Federal Food, Drug, and Cosmetic Act, Virtual Biopharma Inc. hereby certifies that it did not and will not use in any capacity the services of any person debarred under section 306 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 335a) in connection with this application.

This certification applies to all persons whose services were used in connection with the development of the data in, and the preparation and submission of, this application, including employees, contractors, consultants, clinical investigators, and other agents of the applicant. To the best of the applicant's knowledge, no such person is debarred under section 306 of the Act.

The applicant understands that:

1. If the applicant becomes aware, after submission, that any person who was, is, or will be involved in this application is or becomes debarred, the applicant will notify FDA in accordance with applicable requirements.
2. A conviction that would be the basis for debarment, or the knowing use of the services of a debarred person, may render this application not approvable or subject to withdrawal, and may subject the applicant to civil penalties under section 307 of the Act (21 U.S.C. 335b).
3. A knowingly false statement in this certification is a criminal offense under 18 U.S.C. 1001.

Signed: (executed — signature applied) Jane A. Doe, PhD, RAC — Chief Regulatory Officer & Head of Global Regulatory Affairs Virtual Biopharma Inc., 100 Innovation Way, Cambridge, MA 02142 Date: 09 July 2026

1.3.4 Financial Certification and Disclosure (Forms FDA 3454 / FDA 3455)

Submitted pursuant to 21 CFR Part 54 (Financial Disclosure by Clinical Investigators) and 21 CFR 601.2(a).

Virtual Biopharma Inc. has collected financial-interest and arrangement information from all clinical investigators who participated in the clinical study on which this application relies (Study TILA278-201), covering the period from one year before the study through one year following its completion, in accordance with 21 CFR 54.4.

Form FDA 3454 — Certification: Financial Interests and Arrangements of Clinical Investigators

As the applicant, Virtual Biopharma Inc. hereby certifies that it has not entered into any financial arrangement with the listed clinical investigators (and their subinvestigators and spouses/dependent children) whereby the value of compensation to the investigator could be affected by the outcome of the study, as defined in 21 CFR 54.2(a); that each listed investigator was required to disclose whether the investigator had a proprietary interest in this product (21 CFR 54.2(c)) or a significant equity interest in the sponsor (21 CFR 54.2(b)); and that no listed investigator was the recipient of significant payments of other sorts as defined in 21 CFR 54.2(f), except as disclosed on the attached Form FDA 3455.

Certification element	Status
Study covered	TILA278-201 (pivotal Phase 2b induction study)
Number of clinical investigators / subinvestigators covered	148 across 96 sites
Investigators with no disclosable interests (covered by Form FDA 3454)	145
Investigators with disclosable interests (covered by Form FDA 3455)	3

Form FDA 3455 — Disclosure: Financial Interests and Arrangements of Clinical Investigators

For the 3 investigators with disclosable interests, the nature of each interest and the steps taken to minimize the potential for bias are described below. Complete per-investigator disclosures, amounts, and dates are provided in the appended Form FDA 3455 and supporting tables.

Investigator (blinded ID)	Type of disclosable interest (21 CFR 54.2)	Steps taken to minimize bias
INV-014	Significant payments of other sorts (§ 54.2(f)) — advisory/consulting fees exceeding $25,000 exclusive of study costs	Enrolled a small fraction of subjects at a multicenter site; treatment blinded; primary endpoint objectively scored (modified Mayo, central review); sensitivity analysis excluding the investigator's subjects did not alter the primary result
INV-052	Significant equity interest in sponsor (§ 54.2(b)) — equity disclosed conservatively	Blinded, placebo-controlled design; central statistical analysis; independent data monitoring committee oversight
INV-088	Proprietary interest (§ 54.2(c)) — named on a pending patent application relating to TL1A biology	Non-primary contributor to enrollment; objective centrally read endpoints; exclusion-based sensitivity analysis confirmed robustness of efficacy conclusions

For each disclosed interest, the multicenter, randomized, double-blind, placebo-controlled design of Study TILA278-201, the objective centrally scored primary endpoint (clinical remission by modified Mayo), independent data-monitoring oversight, and prespecified sensitivity analyses excluding affected investigators together minimize the potential for these interests to affect the reliability of the data. The efficacy conclusions (dose-ordered clinical remission of 37.3% / 16.2% / 0.7% for High / Low / placebo) are not materially changed by these disclosures.

Signed: (executed) Jane A. Doe, PhD, RAC — Chief Regulatory Officer, Virtual Biopharma Inc. — 09 July 2026.

1.3.5 Patent Information and Certification Statement

Applicability to a 351(a) BLA. This application is submitted under section 351(a) of the Public Health Service Act. The patent-information and patent-certification requirements of sections 505(b)(1), 505(b)(2), and 505(j) of the Federal Food, Drug, and Cosmetic Act, and the "Orange Book" (Approved Drug Products with Therapeutic Equivalence Evaluations) patent-listing framework, do not apply to biological products licensed under section 351 of the PHS Act. Accordingly, no patent declaration under 21 CFR 314.53 and no paragraph I–IV patent certification are submitted with this application. Items 15 and 16 of Form FDA 356h are marked "Not applicable" on that basis.

Biosimilar / BPCIA context. As a reference product licensed under section 351(a), TILA-278, if approved, will be listed in the FDA "Purple Book" (Database of Licensed Biological Products) with its licensure and, where applicable, reference-product exclusivity dates as determined by FDA under section 351(k)(7) of the PHS Act. Any patent disputes relating to future biosimilar applications referencing TILA-278 would be governed by the patent-exchange provisions of the Biologics Price Competition and Innovation Act (BPCIA), 42 U.S.C. 262(l), which are addressed outside of and independently from this licensing application.

Applicant patent statement (informational). For the Agency's information, and without creating any obligation not required for a 351(a) application, the applicant states that TILA-278 and its use in ulcerative colitis are the subject of the following applicant-owned or applicant-licensed patents and applications:

Patent / application	Subject matter	Status
US 11,XXX,XXX	Bispecific anti-TL1A / IL-22R antibody compositions of matter	Granted
US 11,YYY,YYY	Methods of treating inflammatory bowel disease with a dual TL1A-antagonist / IL-22R-agonist antibody	Granted
US 2025/0XXXXXX A1	Subcutaneous formulation and autoinjector presentation	Pending

This statement is provided for completeness only; the applicant does not seek, and this application does not require, any patent-based action by the Agency in connection with the licensure of TILA-278.

---

End of Module 1 forms, cover letter, and certifications for BLA 76XXXX (TILA-278). Cross-references: proposed labeling and Instructions for Use (Module 1.14); pediatric plan (Module 1.9); CMC (Module 3, CHO-derived humanized IgG1 bispecific drug substance; SC prefilled-syringe/autoinjector drug product); nonclinical package consistent with ICH S6(R1), including cynomolgus repeat-dose SC toxicology and tissue cross-reactivity, with no genotoxicity or carcinogenicity studies expected for a monoclonal antibody (Module 4); clinical pharmacology addressing target-mediated drug disposition, SC bioavailability, tiered immunogenicity assessment, and the ICH E14/S7B basis for a QT-study waiver (Module 5.3.1 / 5.3.3); and the pivotal clinical study TILA278-201 (Module 5.3.5).