Spinal Cord Injury Treatment

Política y estrategia empresarial: NFX81: Paralysis treatment in SCI patients NFX88: Neuropathic pain treatment

NFX81 against paralysis Neurofix S.L.

NFX81 Mechanism of Action Precedents: Albumin-Oleic Acid, a Neurotrophic Growth Factor 4

SPINAL CORD INJURY VEHICLE TREATMENT DAY 1 DAY 7

SPINAL CORD INJURY NFX81 TREATMENT DAY 1 DAY 7

Effect of NFX81 against paralysis in SCI rats Vehicle NFX80 NFX81 7

NFX81 MoA: Microarray analysis Neurofix S.L.

NFX81 MoA: Gene Expression Neurofix S.L.

NFX88 against neuropathic pain Neurofix S.L.

Proportion Affected (%) Spinal Cord Injury 4.8 ± 2.9 81 Pain 3.7 ± 2.6 Spasms 4.9 ± 3.6 82 Sexual Function 5.0 ± 3.3 90 Paralysis Difficulty (0-10) Proportion Affected (%) Problem Siddall et al., Pain 103 (2003) 249-257 Worldwide 20,000 new cases of SCI per year, many surviving more than 5 years requiring lifelong treatment that can exceed costs of $1,000,000. Absence of cure or effective medication. Reduced Quality of Life (QOL) and progressively diminishing autonomy. 11

NFX88 for Neuropathic Pain A Large and Underserved Market Neuropathic pain affects 2-3% of the population. The total market reached $5B by 2010 in the US only and $5.3B by 2008 in Europe. Worldwide the neuropathic pain market is > $10B and underserved which makes it very attractive. 2. Neuropathic Pain has a unique etiology and doesn’t respond to conventional analgesics, hence the interest in finding new therapeutic options. En cuanto a que es lo que estamos investigando, nosotros investigando la lesion medular y dentro de la lesion medular nos centramos en el dolor que se produce tras la lesion medular. El dolor normal, en si es un mecanismo fisiologico, que tiene una proporcionalidad entre el estimulo y lo que sentimos y que tiene una funcion eminentemente protectora. Pero el dolor tambien puede ser patologico no protector, y dentro de este tipo de dolor anormal, el que nos interesa es el dolor neuropatico que es aquel que se inicia por una lesion o una disfuncion en el sistema nervioso. Este dolor es mantenido por un procesamiento aberrante de la informacion en el SNP o en el SNC, que siempre se ha relacionado con una hiperexcitabielidad neuronal causante de ese procesamiento aberrante, ademas este dolor no es proporcional al estimulo que lo provoca. 12

NFX88 Electrophysiology Saline NFX80 NFX88 10xNFX80

Oral NFX88 against pain Veh (p.o.) Sham Veh (p.o.) SCI Preg (p.o.) SCI NFX88 (p.o.) SCI Inhibition of the withdrawal reflex induced by acetone in SCI rats. Animals were treated with vehicle (Veh), pregabaline (Preg) or NFX88 (p.o.).

Modulation of nociception with NFX88 The Spared Nerve Injury model von Frey Test and noxious heat reflex Vehicle NFX88 Vehicle NFX88

Modulation of nociception with NFX88 The Spared Nerve Injury model. Hot Plate Test LPA181 + SNI Vehicle NFX88

Modulation of nociception with NFX88 The Spared Nerve Injury model. Cold Plate Test LPA181 + SNI Vehicle NFX88

Modulation of nociception with NFX88 The administration of NFX88 modulates nociception without side effects or alteration of motor function. Treatment of animals with peripheral nerve injury with NFX88 has an important effect on the reduction of mechanical hypersensitivity to mechanical stimuli. NFX88 eliminates thermal heat hypersensitivity. NFX88 prevents the development of hypersensitivity to mechanical stimuli and noxious heat. 18

Neurofix treatments for Spinal Cord Injury NFX81 will start phase I/II studies against paralysis in 2017. NFX88 will start a phase II study against neuropathic pain is SCI patients in 2018. Neurofix will invest € 3m in this project during the next 2 yr. Investment and alliance partners are welcome. En cuanto a que es lo que estamos investigando, nosotros investigando la lesion medular y dentro de la lesion medular nos centramos en el dolor que se produce tras la lesion medular. El dolor normal, en si es un mecanismo fisiologico, que tiene una proporcionalidad entre el estimulo y lo que sentimos y que tiene una funcion eminentemente protectora. Pero el dolor tambien puede ser patologico no protector, y dentro de este tipo de dolor anormal, el que nos interesa es el dolor neuropatico que es aquel que se inicia por una lesion o una disfuncion en el sistema nervioso. Este dolor es mantenido por un procesamiento aberrante de la informacion en el SNP o en el SNC, que siempre se ha relacionado con una hiperexcitabielidad neuronal causante de ese procesamiento aberrante, ademas este dolor no es proporcional al estimulo que lo provoca. 19

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