🔬Day 6 | The Development Journey of Oligo Therapeutics — and Why It Matters for CDMOs

Oligo Therapeutics (siRNA, ASO, miRNA, sgRNA, etc.) are rapidly moving from scientific curiosity to clinical reality.
Yet the development path behind them is often misunderstood — especially how technical risks, material and API needs, and CDMO engagement evolve across stages.
Here is a clear, stage-by-stage breakdown from both a scientific and CDMO perspective:
1️⃣ Target Discovery & Validation
✔The goal is to confirm whether a gene is suitable for nucleic acid intervention.
✔This includes functional knockdown/overexpression, sequence accessibility, tissue expression, and competitive IP analysis.
👉 Not every target is nucleic-acid friendly — this is the first filter.

2️⃣ Sequence Design & Lead Identification
✔This is where nucleic acid therapeutics differ most from small molecules and biologics.
✔Algorithm-driven sequence selection
✔Chemical modifications (2′-OMe, 2′-F, MOE, PS, LNA…)
✔Off-target & immunogenicity prediction
✔In vitro potency screening
👉 The quality of decisions here determines downstream risk and cost.

3️⃣ Delivery System & Formulation
“Good sequence but bad delivery” remains the #1 failure point.
✔GalNAc for liver targeting
✔LNP for systemic delivery
✔Conjugates, polymers, liposomes
👉 Delivery determines whether the molecule reaches the right place at the right time.

4️⃣ Preclinical Development
Now the focus shifts to IND-enabling work:
✔PK/PD
✔Toxicology (repeat dosing, immune activation)
✔Tissue distribution
✔GLP studies in two species
👉 A strong PD signal at this stage is a powerful indicator of future success.

5️⃣ Clinical Development (Phase I–III)
✔Phase I: Safety, PK, tolerability
✔Phase II: Dose & early efficacy
✔Phase III: Confirmation
👉 Many nucleic acid drugs show meaningful PD signals as early as Phase I/II.

6️⃣ CMC & Regulatory
CMC grows in importance with each step:
✔Solid-phase or enzymatic synthesis
✔Impurity profiling
✔Analytical method development
✔Stability
✔IND/NDA submission
👉 The jump from mg → g → kg is where CDMOs truly add value.


💡 Final Thought
Oligo therapeutics represent one of the most exciting and fast-moving fields in drug development today.
For CDMOs, understanding where customers are in the journey and what they need at each stage is key to building meaningful, long-term partnerships.
If you're working in oligonucleotide development or CDMO strategy, I'd love to connect and exchange perspectives.