Novel CYP26B1 inhibitor for topical application

More than 600 million people have acne and it is common in the younger population. Acne is a skin condition that occurs when hair follicles become plugged with oil and dead skin cells. It often causes whiteheads, blackheads or pimples, and usually appears on the face, forehead, chest, upper back and shoulders.

Acne is becoming more common in lower ages and 85% of all 12-24 year old have at least mild acne. Acne is still present up to ages of 40-50. The global market is growing, fastest in USA and Asia-Pacific, and is estimated to be 7 Billion USD in 2025.

Current Standards of Care and their Side Effects

Severe acne is normally treated with oral drugs
Isotretinoin: Amnesteem, Claravis, Sotret, Ruoccotane are powerful drugs used for severe acne that does does not respond to other treatments.
Antobiotics: Erythromycin, Tetracyclins.

Mild and moderate acne is normally treated with topical drugs
Retinoids and retinoid-like drugs. Isotretinoin, Tretinoin (Avita, Retin-A, etc), adapalene (Differin) and tazarotene (Tazorac, Avage).
Antibiotics Clindamycin, Erythromycin.
Antimicrobials Benzoyl peroxide, Salicylic acid and azelaic acid.
These drugs are used either on their own or in combination treatments.

Side effects are often observed when using the current treatments.
Local side effects include erythema, itching, dryness, burning, peeling, and pseudomembranous colitis. Development of resistance is a severe problem when using both antibiotics and retinoids. Retinoid use can also lead to defects in babies when used by their mother during pregnancy.

The C26 solution

  • Highly effective topical treatment of mild to moderate acne with our CYP26B1 inhibitor compound.
  • Acts locally by increasing the natural Vitamin A levels in skin tissue:
    • C26-1 is a small molecule that increases the natural Vitamin A in skin tissue by specifically inhibiting the enzyme CYP26B1.
    • It is thus blocking degradation of cellular Retinonic Acid (RA) in the tissue.
    • This replaces treatment with externally applied RA or antibiotics.
    • C26-1 increases intrinsic Vitamin A levels without entering the systemic circulation thereby reducing teratogenicity.
  • Our data show that C26-1 is not metabolized and does not inhibit Cytochrome P450 enzymes in the liver.
  • C26-1 does not pass the blood-brain-barrier.
  • All tests indicate a very positive ADMET profile.

The mechanism

Metabolism and clearance of RA is mediated by the CYP26A1 and CYP26B1 enzymes that are critical retinoic acid hydroxylases during both fetal development and adulthood, contributing to tissue-specific regulation of RA concentrations and signaling.

CYP26B1 is upregulated and catabolizes RA in damaged / inflamed tissue. Its isoform CYP26A1 is mainly expressed in the liver.

Degradation of RA leads to enhanced cell proliferation; high levels of RA has efficient anti-proliferatory effects. For conditions where high levels of RA are beneficial, current solutions involve use of large amounts of exogenous retinoids, which however are associated with severe side effects.

Development of the C26 Compounds

  • Homology Modeling (A1 and B1)

  • Virtual highthroughput screening

  • Tests in protein and cell based assays

  • IP protection

  • Synthesic Protocols (+analogs)

  • Further tests (Safety, ADMET pred, CYP panel, IC50)

  • NEXT STEP Additional tests, formulations, animal models.

EXAMPLES OF Target validation

Transfected COS-1 cells Synthetic protocol

CONCLUSION
C26 is a powerful inhibitor of CYP26B1

Patent status and analogs

Patent for C26-1 approved in USA, Europe and China. Patent pending in Canada.

Several analogs currently are currently being evaluated.

Investor summary

C26 Bioscience is a start-up company based on research discoveries from Gothenburg and Örebro universities.

MARKET: There is a need for more efficient and safe products. Market size estimated to USD 7 Billion by 2025.

IP: Patent for C26-1 approved in USA January 2020, Europe February 2020, and China February 2022. Several are analogs being developed/evaluated providing potential for additional patents.

STRONG SCIENTIFIC TEAM, and Örebro University Enterprise AB, as co-owner, is providing seed capital investment, drug and business development expertise, and project management competence.

OPPORTUNITY: We are seeking partners for licensing/investment and/or pre-clinical/clinical development.

NOVELTY: The compound, C26-1, inhibits CYP26B1 and blocks degradation of cellular Retinonic Acid (RA) in tissue. This can replace treatment with externally applied retinoids or antibiotics and thus be safe and more effective than current treatments.

INDICATION: Acne, topical treatment with our compound, C26. It exerts its effect by increasing local endogenous Vitamin A levels without increasing the retinoid load in circulation, thus having less side-effects and teratogenicity.

The team

Prof. Åke Strid, Chairman of the Board
Biochemistry, Örebro university
Protein production and enzymology.
>120 publications; ≈4600 citations.

Prof. Allan Sirsjö, CEO
Biomedicine, Örebro university
Cardiovascular disease and mechanisms.
100 publications; 1500 citations.

Prof. Leif A. Eriksson, Board member
Chemistry, University of Gothenburg
Drug design and biomolecular mechanisms/simulations.
>280 publications; >7000 citations.

Peter Blomberg
Innovation advisor / Inkubera Company incubator
Over 20 years of experience of development and quality management as Manager and as
Management Consultant in the technical field.

Consultants in chemistry, drug development and marketing

Contact

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