Precision medicine for
15q11.2 duplication

Longinus Therapeutics is developing a targeted treatment for 15q11.2 BP1-BP2 microduplication — a common, recurrent genetic change affecting families worldwide. Our lead program is a CYFIP1-lowering antisense oligonucleotide (ASO), advanced through a strictly staged, evidence-first plan: confirm the target, then build the drug.

15 BP1 BP2 CYFIP1 ×3 copies 15q11.2
~1 in 500
People carry this duplication
200–600K
Clinically affected globally
3
Genes in the duplicated region
0
Approved targeted treatments

The gap between diagnosis and treatment ends here

Longinus Therapeutics is a Madrid-based precision-medicine biotech founded in 2026 to develop targeted treatments for 15q11.2 BP1-BP2 microduplication. We exist because no one else is building the program — despite a well-understood genetic mechanism, clear preclinical models, and a precedented regulatory path.

The science exists. The CYFIP1 gene is well-characterized. The downstream pathways are druggable. A realistic ASO development timeline is 5–7 years to first patient dosed, 7–9 years to potential approval. What is missing is a focused, well-funded program to make it happen.

We fund the research, own the IP, and are building the data package that can bring a development partner to the table — following the proven rare-disease model: patient-derived science → preclinical data → partnership.

The Target

15q11.2 BP1-BP2 Microduplication

Primary gene CYFIP1 (overexpression ~150%)
Mechanism Dual role: WAVE/actin complex + FMRP–eIF4E translational brake; drives mTOR hyperactivation and NMDA-receptor imbalance
Therapeutic goal Normalise CYFIP1 toward ~110% — never to zero (over-depletion mimics the deletion disorder)
Safety gate CYFIP2 selectivity (~88% identical; CYFIP2 loss → epileptic encephalopathy)
Phenotype Autism, language delay, ID (variable), seizures ~5–8%
Diagnosis Chromosomal microarray (array CGH)
Carrier prevalence ~1 in 500 — one of the most common recurrent CNVs
Clinically affected 200–600K globally (≈5–8% penetrance)
Trial-eligible Children with significant clinical impact — orphan scale

What the duplication does to the brain

The 15q11.2 BP1-BP2 microduplication places an extra copy of CYFIP1 in every cell. CYFIP1 overexpression disrupts two core pathways — NMDA receptor suppression and mTOR overdrive — both confirmed in human post-mortem brain tissue. CYFIP1 is dosage-sensitive in both directions: deletion and duplication each cause disease. That defines our therapeutic principle precisely — lower CYFIP1 back toward the normal range, never to zero. Over-suppression would recreate the deletion disorder, so the goal is dosage normalisation, not silencing.

Two design constraints follow, and both shape the program from day one. CYFIP2 selectivity is a hard safety gate: CYFIP1's paralogue CYFIP2 is ~88% identical, and loss of CYFIP2 causes a severe epileptic encephalopathy — so any candidate must lower CYFIP1 while sparing CYFIP2. And because CYFIP1 is broadly expressed in the body but only its brain dosage drives the phenotype, the program is built around CNS-selective (intrathecal) delivery to act where it matters and limit exposure elsewhere.

Six interconnected biological pathways are perturbed by CYFIP1 overexpression — each offers a potential therapeutic handle. Our program targets CYFIP1 itself at the mRNA level via an antisense oligonucleotide, restoring dosage upstream of every downstream pathway shown below.

15q11.2 BP1-BP2 Duplication +1 extra CYFIP1 copy · ~150% expression PATHWAY 1 · CYTOSKELETON PATHWAY 2 · TRANSLATION PATHWAY 3 · SYNAPSE WAVE Complex Imbalance Rac1/WAVE dysregulation ↑ actin polymerization Abnormal Dendritic Spines Immature morphology Excess density mTOR Overdrive ↑ mTORC1 activity Confirmed in post-mortem tissue FMRP / eIF4E Sequestration CYFIP1 traps eIF4E in repressor Over-suppressed translation NMDA Hypofunction ↓ GluN2A · ↓ GluN2B subunits confirmed in human tissue Impaired Plasticity ↓ LTP · slower learning E/I imbalance · seizure risk Clinical Phenotype Autism · language delay · ID (variable) · seizures CYFIP1-Lowering ASO · upstream root cause correction RNase H-mediated mRNA reduction · restores normal dosage across all three pathways simultaneously

From design to first patient

Our program follows a strictly staged, evidence-first sequence. Money is committed only after each prior step proves out — so the cheapest experiments answer the make-or-break questions before any expensive work begins. Each phase has a defined exit criterion; if the data does not support advancing, the program stops there.

Step 0
Confirm the target
Complete the genetic workup that confirms the duplication is the relevant driver before any target-specific spend. The cheapest gate first — it can reshape or stop the program for the price of a routine test.
Genetics Differential dx
Phase 0
Measure — is the protein actually elevated?
Derive patient iPSC neurons and measure CYFIP1 at the protein level against matched controls. A duplication in the DNA does not guarantee excess protein — this is the true gate on everything downstream. If it is not elevated, the program redirects before any drug spend.
iPSC neurons Protein readout Go / No-Go
Phase 1
Find the molecule
Design and screen candidate ASO sequences in patient neurons; select the lead that lowers CYFIP1 toward normal — with CYFIP2 sparing as a hard selectivity gate — and rescues the cellular phenotype. Only a validated, selective lead unlocks the expensive manufacturing step.
ASO screen Lead selection
Phase 2
Make it real
Clinical-grade manufacturing and the safety (toxicology) package for the selected lead — the regulated, capital-intensive step, commissioned only after the biology is de-risked.
Manufacturing Safety package
Phase 3
Permission & treatment
Assemble and file the regulatory dossier with the competent authority and ethics board; treat and monitor under the appropriate individualized-therapy route, with a development partner engaged to take the program to the wider patient population.
Regulatory Treat & monitor
Why this order

Spend follows proof

Principle Each phase is gated — the cheap questions are answered before the expensive ones.
Step 0–Phase 0 Inexpensive. Either confirms the target is real and elevated, or stops the program early.
Phase 1 Find a validated lead molecule in patient cells before committing to manufacturing.
Phase 2–3 The capital-intensive steps run only once the science holds.
Modality Antisense oligonucleotide — chosen for a proven individualized-therapy path and reversibility.

How the program is built

A focused operation with a clear division of labour: patient-derived science to prove the target, regulated execution to build the drug, and a sponsor that funds the work, owns the IP, and sequences the spend.

01

Patient-derived neurons

Patient iPSC-derived neurons are the human validation model for the program — confirming what is true in patient-specific cells, not only in an animal model. A single characterised cell line is derived once, banked, and shared under controlled agreements with every collaborator.

▸ The validation substrate
02

The science partner

An academic lab with deep expertise in CYFIP1 biology confirms the target in patient cells and validates candidate molecules — the de-risking engine that runs before any expensive regulated work begins.

▸ Confirm the target · validate the molecule
03

Regulated execution

A specialist contract research organization designs and screens the ASO candidates, then carries out clinical-grade manufacturing and the safety package for the selected lead. The inventive work is structured so that the resulting intellectual property is owned by Longinus.

▸ Design · screen · manufacture · safety
04

The sponsor

Longinus funds the research, owns the IP and the data package, and takes formal responsibility for coordination and the regulatory route — building a de-risked asset designed to be advanced to the wider patient population through a development partner.

▸ Fund · own the IP · coordinate

How you can help move this forward

Whether you are a family with a diagnosis, a researcher, or a potential pharma partner — there is a concrete role for you.

Families with a Diagnosis

If your child has a confirmed 15q11.2 BP1-BP2 duplication, connect with us. A patient-derived cell line is the foundation of any future treatment, and your experience helps shape what matters most.

Connect with us

Researchers

We are seeking academic collaborators for patient iPSC-neuron work, target validation, and ASO screening. Funded sponsored-research agreements available.

Collaborate

Partners

We are speaking to mission-aligned partners — patient foundations, philanthropic capital, and biotech operators with rare-disease experience. The program is designed around clear preclinical decision gates, and we are happy to share a detailed development plan under a mutual NDA.

Get in touch

Get in touch

Longinus is a small, focused operation. The fastest way to reach us is email — we read everything and respond personally to substantive inquiries. If you are a family with a diagnosis, a researcher with relevant data, an investor with rare-disease conviction, or a clinician fielding a similar case, please write.

Direct
marcio@longinus.bio
Marcio Diaz · Founder
Madrid · Spain · CET
Founded · 2026
Stage · Preclinical · IP-stage
Families

If your child has a 15q11.2 BP1-BP2 duplication confirmed by microarray, we want to hear from you. We are building a contact registry and can share what is actionable today versus what is in development. No commitment, no sales pitch.

Write to us
Researchers

Patient iPSC-neuron work, target validation, ASO screening. We have a defined target and a focused budget — collaborations move faster than grants.

Propose a collaboration
Partners

For mission-aligned partners — patient foundations, philanthropic capital, biotech operators with rare-disease experience — we are happy to share a detailed development plan and clear preclinical decision gates under a mutual NDA.

Open a conversation
Clinicians

If you are a pediatric neurologist or geneticist who has a 15q11.2 BP1-BP2 carrier on your panel and want to discuss off-label options, biomarker testing, or referral to research, this is the inbox.

Discuss a case
Longinus Therapeutics is in early development. This site is informational and does not constitute medical advice or an offer to sell securities. All clinical decisions should be made with qualified physicians familiar with the BP1-BP2 region.