What changed, and when

Unnatural Products (UNP) announced a research collaboration and licensing agreement with Novartis on 18 Feb 2026, focused on an undisclosed macrocyclic peptide program with potential cardiovascular applications. (Unnatural Products press release, Feb 18 2026)
Economics disclosed: up to $100m in upfront and pre-IND milestone payments, up to $1.7bn in development, regulatory, and commercial milestones, plus tiered royalties (mid-single to low double-digits). (Unnatural Products press release, Feb 18 2026, Reuters, Feb 18 2026)
Novartis will run IND-enabling work, then clinical development, manufacturing, and global commercialization for products from the collaboration. (Unnatural Products press release, Feb 18 2026)

60-second thesis frame

This is an early but meaningful “platform validation” signal: a top-tier pharma is paying nine-figure near-term consideration (upfront + pre-IND milestones) for access to UNP’s AI-enhanced macrocycle engine, while taking on downstream IND, CMC, and global commercialization risk. (Unnatural Products press release, Feb 18 2026, Fierce Biotech, Feb 18 2026)
Confidence should rise if the undisclosed cardiovascular target is genuinely hard-to-drug (not a crowded, commoditizing mechanism) and if UNP can show repeatable oral exposure, target engagement, and clean safety margins at chronic dosing, because oral macrocyclic peptides are positioned as a “bridge modality” between small molecules and biologics but can fail on permeability and manufacturability. (Unnatural Products website, Unnatural Products press release, Feb 18 2026)
Context: macrocyclic peptides are already being pushed into cardiovascular outcomes via other programs, including Merck’s oral PCSK9 macrocyclic peptide MK-0616 in Phase 3, supporting “why now” for big-pharma cardio franchises. (Merck press release, Aug 25 2023, ClinicalTrials.gov NCT05261126)

The seven diligence questions

Clinical

• What is the exact target, biology, and “must-win” translational readout, and is the program differentiated versus the best small-molecule, antibody, or RNA benchmark in that pathway (potency, duration, tissue distribution, safety window)? (Unnatural Products press release, Feb 18 2026)
• What is the repeatability story for oral delivery (not one hero molecule): permeability drivers, efflux liabilities, metabolic stability, food effect expectations, and exposure needed for target engagement at chronic dosing?

Payer or Access

• What is the intended population and line of therapy (primary prevention, secondary prevention, HF, dyslipidemia, metabolic-CV overlap), and does the mechanism aim at surrogate endpoints (LDL-C, biomarkers) or hard outcomes (MACE, hospitalization), because this shifts time-to-value and payer scrutiny?
• What is the likely contracting posture (specialty vs. broad retail), and how sensitive is adoption to “oral convenience” versus injection, given payers often gate premium CV drugs behind step edits unless outcomes or budget impact are compelling?

Ops or Adoption

• Can the macrocycle be manufactured and formulated at a cost-of-goods and quality level consistent with high-volume chronic cardiovascular use (yields, purity profile, scalability, oral solid dose feasibility)?

Competitive

• Is UNP’s discovery loop (AI-guided design + parallel synthesis + direct-to-biology screening) actually creating a defensible moat (speed, hit quality, permeability engineering), or is it converging toward an industry pattern where large pharmas can replicate internally? (Unnatural Products press release, Feb 18 2026, Unnatural Products website)

Team or Cap table

• What are the license boundaries (field, target scope, platform rights, reversion, termination economics), and how does deal structure affect UNP’s need to raise, given Novartis is taking IND and beyond but the “platform company” still needs capital to feed the engine?

Red flags

• The “undisclosed” target later reveals itself as a heavily crowded CV mechanism where oral convenience alone is unlikely to clear payer hurdles or clinical differentiation thresholds. (Reuters, Feb 18 2026)
• Oral PK is not reproducible across series (high intersubject variability, food effect, narrow margin), forcing a pivot to injectable delivery that erodes the core strategic promise UNP markets. (Unnatural Products website)
• CMC reality bites: macrocycle synthesis scale-up or impurity control is harder than expected, making chronic CV pricing and supply reliability untenable even if biology works.

Next catalyst

Watch for incremental disclosure in Novartis public forums, particularly the 06 Mar 2026 AGM and 28 Apr 2026 Q1 results, where pipeline or partnering color sometimes emerges even when targets remain unnamed. (Novartis AGM 2026 event page, Novartis event calendar)

FAQ

• What exactly changed by Unnatural Products’ “Licensing Agreement with Novartis” news on 18 Feb 2026, and why does it matter for Cardiovascular? The two companies formed a $1.8 billion partnership to use AI for designing macrocyclic peptides (GlobeNewswire). This matters because it targets “undruggable” cardiovascular pathways that traditional small molecules cannot reach and biologics cannot access orally (Reuters).
• What is the regulatory path after the 18 Feb 2026 announcement, and what are the next formal steps in the US, UK, and EU?
  Novartis is now responsible for all IND-enabling studies and future clinical development (Morningstar). The next step is a formal Investigational New Drug (IND) filing with the FDA to begin Phase 1 human trials.
• Why are macrocyclic peptides positioned as strategically attractive in the 18 Feb 2026 UNP–Novartis announcement?
  UNP describes macrocyclic peptides as combining biologic-like binding with small-molecule-like delivery potential, including oral delivery in some cases. (Unnatural Products press release, Feb 18 2026, Unnatural Products website)
  The broader field has visible momentum in cardiometabolic risk reduction, including Merck’s oral PCSK9 macrocyclic peptide MK-0616 entering Phase 3 programs. (Merck press release, Aug 25 2023, ClinicalTrials.gov NCT05261126)
• What is UNP’s stated platform approach referenced in the 18 Feb 2026 announcement, and what should diligence focus on?
  UNP says its “integrated discovery engine” combines AI-guided molecular design, massively parallel synthesis, and direct-to-biology screening to generate potent, selective macrocycles for oral or injectable use. (Unnatural Products press release, Feb 18 2026)
  Diligence should stress-test whether that loop yields repeatable oral exposure and scalable CMC, not just compelling binders. (Unnatural Products website)
• When might the market learn more after the 18 Feb 2026 UNP–Novartis announcement?
  The companies did not disclose the specific target or program details in the initial announcement, so near-term color is most likely to come via major Novartis public events and reporting cycles. (Unnatural Products press release, Feb 18 2026, Reuters, Feb 18 2026)
  Two concrete waypoints are the 06 Mar 2026 AGM and 28 Apr 2026 Q1 results on Novartis’ published calendar. (Novartis AGM 2026 event page, Novartis Financial Results Q1 2026)

Publisher / Disclosure

Publisher: LucidQuest Ventures Ltd. Produced: 18 Feb 2026, 20:15 London. Purpose: general and impersonal information. Not investment research or advice, no offer or solicitation, no suitability assessment. UK: directed at investment professionals under Article 19(5) and certain high-net-worth entities under Article 49(2)(a)–(d) of the Financial Promotion Order 2005. Others should not act on this. Sources and accuracy: public sources believed reliable, provided “as is,” may change without notice. No duty to update. Past performance is not reliable. Forward-looking statements carry risks. Methodology: questions-first framework using public sources. No conflicts. Authors do not hold positions unless stated. © 2026 LucidQuest Ventures Ltd.

Entities / Keywords

Unnatural Products (UNP); Novartis; NIBR; Muneto Mogi; Cameron Pye; macrocyclic peptides; macrocycles; oral bioavailability; IND-enabling; cardiovascular disease; chronic disease; drug discovery platform; AI-guided design; parallel synthesis; direct-to-biology screening; royalties; milestones; licensing agreement; PCSK9; MK-0616; enlicitide; ClinicalTrials.gov; CMC; permeability; target engagement; MACE; payer access; formulary; step therapy.

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