Challenges

High Mortality

In low- and middle-income countries ("LMICs"), prostate cancer is one of the leading causes of death, and in many countries of the Global South there is literally no affordable standard of care treatment. The number of cases has been increasing in recent decades, and the Lancet Commission on prostate cancer predicts that it will double between 2020 and 2040.
(see publication below)

"Impact-First" Approach

This philanthropic initiative is not structured for financial gain, but for maximizing health impact in underserved regions, a concept which does not align with the objectives of commercial investors. Conventional routes of drug development rely on patent protection to ensure marketing exclusivity and high financial returns.
With off-patent drugs like Terbinafine, there is very limited commercial appeal to seeking broader use and therefore no motivation to invest in additional clinical trials.

The Lancet Commission on prostate cancer: planning for the surge in cases

The Lancet Commissions Volume 403, Issue 10437 p1683-1722 April 27, 2024 https://doi.org/10.1016/S0140-6736(24)00651-2

SCIENCE

A Strong Case for Development in Oncology

Terbinafine was invented in 1980 by Anton Stütz at the Sandoz Research Institute in Vienna, Austria. It was developed as an antifungal medication and is considered one of the gold standard treatments for fungal infections globally. Over the past 30 years, it has been instrumental in helping countless patients around the world cure fungal infections of the skin and nails. The drug is highly safe and well-tolerated in its current use, with serious side effects being extremely rare. More than 100 million patients have successfully used it daily for several months to treat persistent nail infections.

It belongs to a class of drugs known as allylamine antifungals, which work by inhibiting the enzyme squalene epoxidase (SQLE) in fungi. It disrupts the synthesis of ergosterol, which is crucial for maintaining fungal cell membrane integrity and function. Inhibition of SQLE in fungal organisms leads to several critical consequences that ultimately result in the death of the fungal cell.
In humans, SQLE is critical in the synthesis pathway of cholesterol, the molecule corresponding to fungal ergosterol. Terbinafine binds to human SQLE with only very low affinity and does not affect cholesterol metabolism. In contrast to another class of drugs, azole antifungals it does not lower cholesterol or alter hormone levels in humans.

Recent and new emerging evidence suggests that SQLE plays a crucial role in cancer cell metabolism, indicating that Terbinafine may be beneficial in treating prostate, colorectal, breast, hepatocellular, squamous cell, and other types of cancer. Numerous studies have established that Terbinafine inhibits the proliferation of cancer cells, blocks tumor growth in cancer models and significantly reduces prostate cancer mortality.

Selected Publications:

Use of Terbinafine and risk of death in patients with prostate cancer

J. Ji, J. Sundquist, Kr. Sundquist; IJC (2018)

https://doi.org/10.1002/ijc.31901

Analysis of patients treated with Terbinafine for concurrent fungal infections shows a 47% decrease in prostate cancer mortality compared to patients who did not use Terbinafine.

MiR-205-driven downregulation of cholesterol biosynthesis through SQLE-inhibition identifies therapeutic vulnerability in aggressive prostate cancer

Kalogirou, c. et al.; Nature Commun. (2021)

https://doi.org/10.1038/s41467-021-25325-9

This publication in the leading scientific journal Nature reports that (i) SQLE is overexpressed in advanced prostate carcinoma linked with poor survival, (ii) Terbinafine inhibits prostate cancer cells and blocks tumor growth in prostate cancer models in vivo, (iii) late-stage prostate cancer patients concurrently treated with Terbinafine off-label show reduced PSA levels.

Squalene Epoxidase: Its Regulations and Links with Cancers

Zhao, X et al.; Adv Sci (2023)

https://doi.org/10.3390/ijms25073874

This recent review highlights the role of squalene epoxidase, the therapeutic target of Terbinafine, also in additional cancers and concludes: “The anti-tumor effect of Terbinafine has been observed when treating breast cancer, non-small-cell lung cancer, hepatocellular carcinoma, leukemia, colorectal carcinoma, prostate cancer, pancreatic cancer, and oral squamous-cell carcinoma“.

Targeting Squalene Epoxidase Confers Metabolic Vulnerability and Overcomes Chemoresistance in HNSCC

Zhang, L. et al.; Int. J. Mol. Sci. (2024)

https://doi.org/10.1002/advs.202206878

Cisplatin resistance poses a substantial hurdle in effectively treating head and neck squamous cell carcinoma. Utilizing multiple tumor models and examining an internal HNSCC cohort, SQLE is identified as a key driver of chemoresistance and tumorigenesis. The preclinical findings demonstrate the potent synergistic effects of combining Terbinafine and cisplatin in arresting tumor growth.

GOALS & STRATEGY

Goals

With this initiative, we aim to

1. To investigate the efficacy and safety of Terbinafine as a treatment for prostate cancer.

2. Democratize access to cancer treatment globally by developing an affordable therapeutic modality, making treatment accessible to hundreds of millions of people thus significantly reducing cancer mortality rates and improving quality of life in LMICs.

3. Contribute to the improvement of local health infrastructure through participation (preparation, performance, analysis, etc.) in high-level development programs, strengthening their long-term capacity and competence to tackle other complex health issues.

4. Make a lasting contribution to global health equity by setting a precedent for a new kind of international collaboration on advanced R&D projects.

Strategy

Our top priority is to strive for the highest level of data quality to facilitate fast approval by regulatory authorities. We have therefore built a team of highly professional and experienced drug development experts to ensure these criteria are met.

We are currently planning to run a series of clinical trials to demonstrate the efficacy of Terbinafine in prostate cancer and, concurrently, to evaluate and prepare an expansion to other cancer indications as we proceed.

Clinical trials will be run in Europe, as well as in countries of the Global South, where the standard of care is different, providing data on various settings and disease stages.

FUNDING & PARTNERING

Conventional routes of drug development rely on patent protection to ensure marketing exclusivity and high returns for originators and investors. With off-patent drugs like Terbinafine, of which low-cost generic versions have been available since 2007, there is very limited commercial appeal to seeking broader use and therefore investing into additional clinical trials.

Our project team has decided to ignore this fact and to develop Terbinafine as if it were a state-of-the-art development candidate, the only difference being that instead of maximizing sales and return on investment we choose to maximize impact by developing the most affordable new cancer drug ever.
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As a nonprofit initiative, we therefore rely heavily on philanthropic and charitable funding or other forms of grants. We welcome partnerships with foundations, charitable organizations, and other entities committed to global equity and invite you to get in touch with us here to discuss potential contributions and/or collaborations.
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TEAM

Anton Stütz

Senior Scientific Advisor and inventor of Terbinafine

40 years in drug R&D and management (Novartis, former Executive Director Dermatology). He is the inventor of the antifungal block buster drug Terbinafine (Lamisil®), the dermatological use of calcineurin inhibitors, and the leading scientist for R&D of pimecrolimus (Elidel®). He has received national and international rewards for innovative therapy of the skin.

Lukas Kadawy

CEO

In his corporate roles, he helped manage the growth of companies from start-up to grown-up stages, with projects ranging from early-stage research projects, across mid- to late-stage clinical programs all the way through to marketing authorization (Qarziba® for the treatment of neuroblastoma).

Bernhard Peball

COO

Started his career at Sandoz/Novartis from 1992 to 1999 in several workgroups. He is an expert in laying the groundwork for scientific operations, having been involved in the setting up of several Vienna-based biotech companies. In his most recent role, he led a device development program in oncology, and was responsible for GMP-ready process development and tech-transfer to CMOs.

Stefanie Fischer

Principal Medical Advisor

As an experienced Medical Oncologist in the field of genitourinary cancers, she has been an active member of the Testicular Cancer Guideline Panel of the European Association of Urology (EAU) for several years. Stefanie has acted as principal investigator in various national and international trials in prostate cancer and early development for new prostate cancer drugs.

Ulrich Granzer

Regulatory Advisor

CEO of one of the world’s leading regulatory consulting companies. Ulrich and his company perform over 150 Scientific Advice meetings (incl. FDA and EMA) per year. Previously he held various regulatory management positions in industry (e.g. Bayer, BASF, Glaxo)

Friedrich K. Mayer

Drug Development Advisor

As Global Project Leader at Novartis Basel, Friedrich built and led multidisciplinary global project teams taking 6 NMEs from research through registration to life cycle management. He has extensive experience in dermatology, infectious diseases and immunology.

THE WORLDWIDE NUMBER OF PROSTATE CANCER CASES IS EXPECTED TO DOUBLE BETWEEN 2020 AND 2040.

MEN OF AFRICAN DESCENT ARE MOST AFFECTED.

But what if …

If you want to support this initiative,
please contact us

With your support

Terbinafine could possibly change the lives of millions of people