Company of the Week: Dayra Therapeutics
Dayra Therapeutics is a Toronto-based biotech company developing oral macrocyclic peptide drugs for immunological diseases. The company launched in November 2025 with approximately $70 million in committed funding, comprising a $50 million upfront payment from Biogen and a $20 million equity commitment from Versant Ventures.
The company emerged from Versant's Frontier Discovery Engine in Canada. Leadership includes acting CEO Rami Hannoush (Versant venture partner) and CSO Roger Palframan, who spent 18 years at UCB Pharma.
Company Overview
| Attribute | Detail |
|---|---|
| Founded | 2024 |
| Headquarters | Toronto, Canada (US corporate registration) |
| Stage | Preclinical |
| Total Funding | ~$70 million |
| Lead Investor | Versant Ventures |
| Strategic Partner | Biogen |
| Focus | Oral macrocyclic peptides for immunology |
Pipeline and Technology Platform
Dayra's pipeline targets clinically validated immunological targets using macrocyclic peptide drug candidates. The company has not disclosed specific targets. The Biogen collaboration covers multiple immunology programs, with Biogen holding options to acquire each resulting program for additional payments plus development and commercial milestones.
During its seed R&D phase, the team advanced macrocyclic molecules against targets in immunology and other therapeutic areas. No specific drug candidates have been announced and no clinical trials are underway.
The Biology of Macrocyclic Peptides
Macrocyclic peptides occupy a pharmacological space between small molecules and antibodies. The modality addresses a structural limitation: protein-protein interaction surfaces in cytokine signaling are flat and large compared to the deep binding pockets that small molecules typically require.
Molecular Size Comparison
| Modality | Molecular Weight | Binding Surface Area | Cell Permeability | Oral Potential |
|---|---|---|---|---|
| Small molecules | <500 Da | 300-500 Ų | High | High |
| Macrocyclic peptides | 500-2,000 Da | 800-1,400 Ų | Variable | Possible with modifications |
| Antibodies | ~150,000 Da | >1,500 Ų | None | None |
The fundamental challenge is that approximately 50% of protein-protein interaction interfaces have non-regular secondary structure. These surfaces lack the concave pockets where small molecules bind effectively. Antibodies can engage these targets but cannot cross cell membranes or survive oral administration.
Why Cyclization Matters
Constraining a peptide into a ring structure produces several effects:
| Property | Linear Peptide | Cyclic Peptide |
|---|---|---|
| Conformational entropy | High | Reduced |
| Protease susceptibility | High | Reduced |
| Target binding affinity | Lower (entropic penalty) | Higher (pre-organized) |
| Membrane permeability | Poor | Improved (with modifications) |
| Oral bioavailability | <1% | Up to 30% (with optimization) |
When peptide ends are joined, the molecule's conformational entropy drops. This pre-organizes the three-dimensional shape, reducing the entropic penalty upon target binding while simultaneously shielding peptide bonds from proteolytic enzymes.
Chemical Modifications for Oral Delivery
Oral peptide delivery requires overcoming enzymatic degradation and membrane permeability barriers. Several modifications improve these properties:
| Modification | Effect | Example |
|---|---|---|
| N-methylation | Reduces hydrogen bond donors, improves membrane permeability | Cyclosporine A has 7 N-methylations |
| D-amino acids | Resists protease cleavage | Common in synthetic macrocycles |
| Non-canonical amino acids | Improves stability, reduces immunogenicity | Platform-dependent |
| Lipophilic modifications | Increases membrane permeability | Decanoate conjugation (MK-0616) |
Cyclosporine A serves as the foundational proof-of-concept: a 1,202 Da cyclic undecapeptide achieving approximately 30% oral bioavailability despite exceeding Lipinski's Rule of 5 molecular weight limit by more than double. The drug's seven backbone N-methylations enable a phenomenon called "chameleonicity"—the molecule adopts different conformations in aqueous versus lipid environments, exposing or shielding polar groups as needed.
Chameleonicity and Membrane Crossing
Successful oral macrocycles exhibit conformational flexibility that enables passive diffusion across lipid membranes:
| Environment | Conformation | Polar Group Exposure |
|---|---|---|
| Aqueous (GI tract lumen) | Open | Exposed (maintains solubility) |
| Lipid membrane | Closed | Shielded (enables permeation) |
| Aqueous (bloodstream) | Open | Exposed (maintains distribution) |
This dynamic behavior allows compounds exceeding 600 Da molecular weight to achieve oral absorption—contrary to conventional drug-likeness predictions.
Immunology Target Landscape
The immunology biologics market generates approximately $100 billion in annual revenue globally. TNF-α inhibitors alone represent a $41-44 billion market.
Key Immunology Targets Currently Requiring Biologics
| Target | Disease Indications | Current Standard of Care | Market Size |
|---|---|---|---|
| TNF-α | RA, psoriasis, IBD, AS | Adalimumab, infliximab, etanercept | $41-44B |
| IL-17A | Psoriasis, PsA, AS | Secukinumab, ixekizumab | ~$10B |
| IL-23 | Psoriasis, IBD, PsA | Risankizumab, guselkumab | ~$8B |
| IL-6 | RA, giant cell arteritis | Tocilizumab, sarilumab | ~$5B |
| CD20 | RA, lupus, MS | Rituximab, ocrelizumab | ~$12B |
These targets require biologics because their protein-protein interaction surfaces are flat and extensive. The IL-17A/IL-17 receptor interface, TNF-α/TNF receptor binding site, and IL-23/IL-23 receptor complex all present binding surfaces exceeding 1,500 Ų.
JAK Inhibitors: The Oral Alternative That Faltered
JAK inhibitors (tofacitinib, baricitinib, upadacitinib) demonstrated that oral drugs could compete with injectable biologics in rheumatoid arthritis, psoriasis, and inflammatory bowel disease. However, the September 2021 FDA black box warning—based on the ORAL Surveillance trial—damaged the class commercially.
| Risk Category | Finding |
|---|---|
| Major adverse cardiovascular events | Increased risk |
| Venous thromboembolism | Increased risk |
| Malignancies | Increased risk (lymphoma, lung cancer) |
| All-cause mortality | Increased risk |
JAK inhibitors are now restricted to patients who have failed or cannot tolerate TNF blockers. This creates an opening for oral macrocyclic peptides that might achieve similar efficacy with different safety profiles.
Partnerships and Investment
Biogen Collaboration Structure
Under the strategic research collaboration announced November 24, 2025:
| Component | Terms |
|---|---|
| Upfront payment | $50 million |
| Program options | Biogen can acquire programs for additional upfront payments |
| Milestones | Development and sales milestones (undisclosed) |
| Development responsibility | Biogen leads post-option |
| Manufacturing | Biogen |
| Commercialization | Biogen |
Biogen's head of research, Jane Grogan, characterized the deal as adding another potential approach to treat immunological conditions.
Versant Ventures Investment
Versant's initial equity commitment of approximately $20 million provides runway for an early-stage biotech. No other investors have been publicly disclosed.
Versant manages $5.5 billion and has completed over 100 exits through IPO or M&A. The firm operates three Discovery Engines:
| Location | Name | Founded | Size |
|---|---|---|---|
| San Diego | Inception | 2011 | 25 scientists, 20,000 sq ft |
| Basel | Ridgeline | 2017 | 40+ scientists |
| Toronto/Montreal | Frontier | Recent | Source of Dayra |
Notable Versant exits include Audentes Therapeutics ($3.0B to Astellas, 2019), Vividion Therapeutics ($1.5B upfront + $500M milestones to Bayer, 2021), and Monte Rosa Therapeutics (IPO June 2021; subsequent $150M upfront/$2.1B milestone deal with Novartis).
Competitive Landscape
Oral Macrocyclic Peptide Companies
| Company | Location | Funding/Deals | Stage | Key Partners |
|---|---|---|---|---|
| Unnatural Products | Belgium | $1.5B deal (argenx), $220M deal (Merck) | Discovery | argenx, Merck |
| Orbis Medicines | Denmark | €116M total (€26M seed + €90M Series A) | Discovery | NEA, Eli Lilly, Novo Holdings |
| PeptiDream | Japan | Multiple pharma deals totaling >$6B in milestones | Discovery/Clinical | Novartis, Merck, Lilly, Roche |
| Bicycle Therapeutics | UK | ~$500-570M market cap, $793M cash | Phase 1/2 | Genentech, Novartis, Ionis |
| Dayra Therapeutics | Canada | ~$70M | Discovery | Biogen |
Unnatural Products Deal Economics
The argenx partnership (July 2025) provides:
| Component | Value |
|---|---|
| Upfront | Double-digit millions (undisclosed) |
| Research milestones | Undisclosed |
| Development milestones | Undisclosed |
| Regulatory milestones | Undisclosed |
| Commercial milestones | Undisclosed |
| Total potential | Up to $1.5 billion |
| Royalties | Tiered on net sales |
Unnatural Products previously secured a $220 million deal with Merck (January 2024) for an oncology target.
Orbis Medicines Funding
Orbis was founded by Christian Heinis (co-founder of Bicycle Therapeutics) and Sevan Habeshian. The company's platform can generate hit-finding libraries of 100 billion compounds. Former Pfizer CSO Mikael Dolsten chairs the board.
Clinical Validation: Merck's MK-0616
Merck's oral macrocyclic peptide PCSK9 inhibitor (MK-0616, enlicitide decanoate) is the most clinically advanced program in this modality class. Phase 2b data showed 60.9% LDL-C reduction at the highest dose. Phase 3 trials (CORALreef program) include approximately 17,000 participants.
Approved Oral Macrocyclic/Peptide Drugs
| Drug | MW | Approval | Oral Bioavailability | Technology |
|---|---|---|---|---|
| Cyclosporine A (Neoral) | 1,202 Da | 1983 | 20-30% | Natural N-methylation |
| Voclosporin (Lupkynis) | ~1,200 Da | 2021 | Improved vs. cyclosporine | Modified cyclosporine |
| Oral semaglutide (Rybelsus) | 4,113 Da | 2019 | 0.8-1% | SNAC enhancer |
| Oral octreotide (Mycapssa) | 1,019 Da | 2020 | ~0.7% | TPE® enhancer |
Biogen's Immunology Strategy
Biogen's immunology expansion reflects diversification away from its neuroscience concentration. CEO Christopher Viehbacher stated in April 2024 that neuroscience alone is insufficient for a company of Biogen's size given the high-risk nature of the therapeutic area.
Biogen Immunology Pipeline
| Asset | Mechanism | Stage | Indication | Deal Terms |
|---|---|---|---|---|
| Felzartamab | Anti-CD38 | Phase 3 | Kidney transplant rejection, IgAN, PMN | $1.15B upfront (HI-Bio acquisition) |
| Litifilimab | Anti-BDCA2 | Phase 3 | SLE, CLE | Internal; Royalty Pharma $250M R&D funding |
| Dapirolizumab pegol | Anti-CD40L | Phase 3 | SLE | UCB collaboration (since 2003) |
| Vanqua oral C5aR1 | Small molecule | Preclinical | Undisclosed | $70M upfront (up to $1.06B total) |
| Dayra programs | Oral macrocyclic peptides | Discovery | Immunology | $50M upfront |
Biogen reported $9.68 billion in 2024 revenue with $2.4 billion cash and $2.7 billion annual free cash flow.
Current Status (December 2025)
Dayra is a preclinical-stage company in the early phases of execution. The Biogen collaboration is in its initial stages—teams are working to identify, validate, and optimize lead compounds against selected immunology targets.
The current phase involves:
| Activity | Status |
|---|---|
| Lead identification | Ongoing |
| Lead optimization | Ongoing |
| Target validation | In collaboration with Biogen |
| IND-enabling studies | Not yet started |
| Clinical trials | None |
| Regulatory filings | None |
Lab operations through the Versant Frontier Discovery Engine in Toronto/Montreal are underway. The company has sufficient capital for the current stage and a defined mandate to produce viable drug candidates.
Blue Team Analysis – Strengths & Opportunities
Platform addresses a known pharmacological gap. Macrocyclic peptides can engage protein-protein interaction surfaces that small molecules cannot effectively bind. If the approach works, oral drugs could replace injectable biologics for chronic immune diseases—a patient preference documented at 73%+ for oral administration.
Non-dilutive funding at inception. The $50 million Biogen upfront payment provides capital without equity dilution. Combined with the Versant commitment, total funding of approximately $70 million is substantial for a discovery-stage company.
Validation from Biogen due diligence. Biogen's willingness to commit $50 million upfront indicates the platform passed scientific and commercial review. This serves as third-party validation for subsequent financing or partnership discussions.
Versant's operational infrastructure. The Discovery Engine model provides wet lab facilities, scientific personnel, and operational support that would otherwise require significant capital and time to establish.
Market size supports the risk profile. The immunology biologics market exceeds $100 billion annually. Even modest market share capture by an oral alternative would generate substantial revenue.
Pipeline optionality beyond Biogen targets. Dayra has indicated work on targets outside immunology during its seed phase, providing additional shots on goal independent of the Biogen collaboration.
Red Team Analysis – Challenges & Risks
Unproven modality in immunology. Oral macrocyclic peptides have not yet demonstrated clinical success in autoimmune or inflammatory diseases. The approach works for cyclosporine (immunosuppression) and MK-0616 (PCSK9/cardiovascular), but these are different target classes with different pharmacological requirements.
Pharmacokinetic challenges are substantial. Achieving adequate oral bioavailability, tissue distribution, and target engagement simultaneously is difficult. Many programs have failed on one or more of these parameters. Dayra's approach remains unvalidated in published preclinical data.
Long timeline to value inflection. Discovery-stage programs typically require 1-2+ years to reach IND filing, then several additional years through clinical development. Capital requirements will increase substantially, and future financing is not guaranteed.
Competitive pressure from well-funded peers. Unnatural Products ($1.5B argenx deal), Orbis Medicines (€116M raised, Eli Lilly backing), and PeptiDream (multiple pharma partnerships) are pursuing similar approaches with significant resources. First-mover advantages in target space and IP position matter.
Target efficacy uncertainty. Even with validated targets, a new modality may not reproduce the efficacy of existing biologics. Macrocyclic peptides might achieve binding without sufficient functional inhibition, or might not reach adequate concentrations at disease sites when given orally.
Partner dependency. The Biogen collaboration provides funding but creates structural dependency. Changes in Biogen's strategy, leadership, or financial position could affect the collaboration's priority. If Biogen declines options, programs may be perceived as "passed over" by potential licensees.
Manufacturing complexity. Macrocyclic peptides can be difficult to synthesize at scale, particularly those incorporating non-canonical amino acids. CMC challenges could delay development timelines or increase costs.
Conclusion
Dayra Therapeutics represents an early-stage bet on the oral macrocyclic peptide modality applied to immunology targets. The company has assembled standard success factors for a discovery-stage biotech: validated scientific leadership, strategic pharma partnership, and experienced venture backing.
The thesis rests on whether macrocyclic peptides can achieve oral bioavailability, adequate pharmacokinetics, and sufficient target engagement to compete with injectable biologics in immunology. This remains unproven. The competitive landscape includes well-funded companies pursuing similar approaches, and clinical validation beyond PCSK9 inhibition is lacking.
The Biogen partnership provides capital and development infrastructure but also creates dependency. The next 18-24 months will likely determine whether Dayra's platform generates drug candidates suitable for IND-enabling studies.
For pharmaceutical royalty investors, Dayra represents the earliest stage of potential royalty-generating assets—discovery programs that, if successful, would generate royalties only after successful clinical development, regulatory approval, and commercialization, likely 8-12+ years from the current date.
Disclaimer: I am not a lawyer or financial adviser. This content does not constitute investment advice, legal advice, or any other form of professional advice. Information is drawn from publicly available sources that may have changed since publication. Conduct your own due diligence before making any investment decisions.
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