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How TheraCryf is advancing the treatment of high unmet need in oncology and behavioural brain disorders

TheraCryf has a broad clinical and preclinical pipeline in oncology and behavioural brain disorders in indications including neurodevelopmental disorders, glioblastoma*, addiction, anxiety, fatigue and narcolepsy*

TheraCryf works closely with major universities, hospitals and government organisations including Erasmus Medical Centre, Kings College London, La Sapienza (Università di Roma), University of Michigan, The Christie and the University of Manchester, University of Auckland, University of L’Aquila, and University of Connecticut to support its research.

*orphan indications
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TheraCryf's most advanced product: SFX-01

There is a significant and growing body of academic research and clinical trials evidencing the increasing relevance of sulforaphane in the treatment of diseases and conditions, including many cancers, where there is a high level of unmet need.   This work has been conducted either with frozen botanical extracts containing unstable sulforaphane (requiring storage at -20°C) or ambient temperature botanical extracts containing glucoraphanin, the chemical precursor of sulforaphane.


Evgen Pharma’s Sulforadex® technology synthesises sulforaphane into an active, stable, and solid form pharmaceutical ingredient, unlocking its medical and commercial potential.  SFX-01, the first product to use  our  Sulforadex® technology, is a complex of sulforaphane and alpha-cyclodextrin formulated as a stable tablet. It has a comprehensive intellectual property package covering its novel compositions and manufacturing methods.

Targets

TheraCryf is focused on developing products to address areas of high unmet need in oncology and behavioural brain disorders.

SFX-01

  • STAT3 and pSTAT3 – STAT3 (signal transducer and activator of transcription 3) and phospho STAT3 (pSTAT3) has importance in controlling cancer metastases. Malfunction in these pathways has been implicated in a number of cancers including breast cancer. Research is ongoing into the role of SFX-01 and its inhibition of STAT3/ pSTAT3 in relation to the development of resistance to other therapeutic options.

  • Nrf2 (nuclear factor erythroid 2-related factor 2) is a transcription factor that is associated with a broad range of diseases characterised by excessive oxidative stress. Nrf2 regulates many target genes including those used in encoding proteins involved in the cellular antioxidant response, damage repair, protein homeostasis and maintenance of metabolic balance. SFX-01 inactivates a protein associated with regulating Nrf2, known as KEAP1 (Kelch-like ECH-associated protein 1), allowing accumulation of Nrf2 and an increase in expression of target genes, potentially improving the cellular response to inflammatory and fibrotic challenges.

  • SHP2 (Src homology-2 domain-containing protein tyrosine phosphatase-2) is involved in several cancer-related processes, including cancer cell invasion and metastasis, apoptosis, DNA damage, cell proliferation, cell cycle and drug resistance. SHP2 may therefore be a therapeutic target of great potential.  In-vitro and in-vivo data demonstrates that SFX-01 modifies SHP2, inhibiting its phosphatase activity which is implicated in many aspects of solid tumour and haematological cancers.


Highly Selective Orexin 1 Receptor Antagonist (Ox-1)

Orexin has a role in reward, feeding behaviour & anxiety and, via the Ox2 receptor, also has a role in sleep. Receptors are found in the hypothalamus, enteric nervous system and gut. Orexigenic signalling via the Ox1 receptor has been implicated in several addictive disorders including binge eating disorder (BED) and alcohol use disorder (AUD).

Proof of concept data has been generated in a rodent model of BED with TheraCryf’s candidate Ox1 antagonist.

Clinical trials using orexin 1 antagonists have demonstrated alleviation of panic and anxiety in human models of these conditions.

 

Atypical Inhibitor of the Brain Dopamine Active Transporter (DAT)

Dopamine has a role in alertness amongst its other  functions in the central nervous system.  A gradual increase in brain dopamine without fast release of dopamine (as caused by amphetamines) is expected to cause alleviation of symptoms of fatigue and narcolepsy.

Proof concept data has been generated in rodent models of fatigue and of narcolepsy using TheraCryf’s candidate atypical DAT inhibitor.