Eusol and Kringle Pharma

[LukeTheDuke]

To the best of my knowledge Eusol and Kriingle Pharma have not received much attention here -- would like to get your perspective on the advancements of these two companies; have you heard of them? Do you think it is promising? Any additional information available?

Eusol -- they are already in phase III
https://en.eusol-biotech.com.tw/service.php

"ES135 is a recombinant human acidic fibroblast growth factor (rhFGF1) with 135 amino acids. With its effect to promote neurite outgrowth, ES135 can be applied to the medical use of repairing neuron function. The sequence of ES135 has been patented in Taiwan, EU, China and the United States. A multi-center, double blind, randomized, placebo control study as the pivotal Phase 3 clinical trial for spinal cord injury is on-going."

Kringle Pharma -- completed phase I/II for acute SCI (hopefully it can be translated to chronic SCI)
http://www.kringle-pharma.com/en/


"Phase I/II study of recombinant human HGF, KP-100IT, for acute spinal cord injury was completed, and the clinical study report has been issued. The positive results of this study will be published later in a scientific journal and presented at academic conferences."
"KP-100IT, recombinant human HGF for the treatment of acute spinal cord injury, was designated as an orphan drug in Japan as of September 12, 2019, with the approval of the Minister of Health, Labor and Welfare."

[FellowHawkeye]

Very interesting. I tried emailing the place in Taiwan and email was rejected. We may need more local people to help us find out more about them....

[Jyi]

The inventor of ES135 is Henrich Chen, he has been mentioned in CC forum many times.
https://www.ym.edu.tw/phd/HCheng_new.htm


For your reference:
http://www.cpmda.org.tw/news_show_n1.php?news_id=8706

("雅祥" = Eusol, "華碩" = ASUS, yes, a notebook big manufacturer, "鄭宏志"= Henrich Chen. Sorry my poor English, Google translation please. )

The effects of ES135..........,no comments.

[FellowHawkeye]

Thanks, jyi! What is considered 'serious spinal cord injury'? I think they all are serious heh. Wouldn't it be a good idea to try drug on people who could respond better such as incomplete injuries? -Jan

[Jyi]

Thanks, jyi! What is considered 'serious spinal cord injury'? I think they all are serious heh. Wouldn't it be a good idea to try drug on people who could respond better such as incomplete injuries? -Jan

It's a machine translation error, 嚴重的脊髓損傷 'serious' should be corrected by 'severe'.

[FellowHawkeye]

It's a machine translation error, 嚴重的脊髓損傷 'serious' should be corrected by 'severe'.

Okay, then completely paralyzed...

[lunasicc42]

GRAMMY or jyi or anyone, everytime I see the eusol listing on the clinicaltrials website I see that it is in phase 3, so I assume they have at least decent phase 2 results, can anyone find them published anywhere?

[GRAMMY]

GRAMMY or jyi or anyone, everytime I see the eusol listing on the clinicaltrials website I see that it is in phase 3, so I assume they have at least decent phase 2 results, can anyone find them published anywhere?

This publication mentions the two acute treatments discussed in this thread. LINK (free access) Time is spine: a review of translational advances in spinal cord injury

The one specific to Eusol Phase 3 is on page 9 in Table 3 (TABLE 3. Summary of active phase III RCTs for traumatic SCI) and discussion page 10.
ES135/rhFGF1
3 Active Centers in (Taiwan)
Patient target: 100
Age 18-65 yrs;
AIS grade A
Intervention: ES 135 administered intrathecally
Control: Placebo administered intrathecally
Primary Outcome: Change in ASIA motor score at 48 weeks

ES135/rhFGF1

Fibrin glue containing acidic fibroblast growth factor(aFGF) has been studied as a possible repair strategy for SCI. In animal studies, aFGF, in conjunction with a peripheral nerve graft, has demonstrated potential to support axonal regeneration and formation of white matter to gray matter connections.24,101 This was tested in a human for the first time in 2004.25 The patient was a young male with chronic paraplegia and a complete spinal cord gap resulting from a stabbing injury. The technique involved bridging the spinal cord gap with sural nerve grafts and applying fibrin glue mixed with aFGF to the grafted area.This patient improved from being wheelchair-bound to being able to ambulate independently with a walker. A phase I pilot study tested local application of fibrin glue with aFGF without nerve grafting in 9 patients with chronic SCI (> 5 months).180 The procedure was well tolerated,and the patients demonstrated significant improvement in ASIA motor and sensory scores. In a subsequent larger trial that involved 49 chronic SCI patients, application of aFGF with fibrin glue and duraplasty performed via laminectomy was combined with adjuvant booster treatment of combined aFGF and fibrin glue at 3 and 6 months post surgery via lumbar puncture.179 Again, the use of aFGF was found to be safe and feasible; significant improvements were seen in ASIA motor and sensory scale scores, AIS grade, neurological level, and Functional Independence Measure (FIM) score at 24 months after treatment. A phase III multi-center, double-blinded, placebo-controlled,randomized trial of aFGF (ES 135; EUSOL Biotech Co.,Ltd.) is currently enrolling patients (NCT03229031). Eligible patients are 18 to 65 years of age and have an AIS A SCI. The target enrollment is 100 patients. The primary outcome is change in ASIA motor score at 12 months.

The Kringle Pharma: Table 2: Page 6. (TABLE 2. Summary of select, ongoing therapeutic phase I/II trials for traumatic SCI)

KP-100IT (HGF)
Kringle Pharma Inc.
Subjects: 48
Age 18-75 yrs;
modified Frankel grade A,B1, or B2; neurological level below C3
HGF intrathecal 0.6mg at 72 hrs; repeat wkly ?5
Control: Placebo at 72 hrs;repeat wkly 5AEs over 24 wks;
ASI A motor score at 24 wks
P-100 concentration in plasma & CSF at 6 wks;
ASIA motor score at 12 wks;
ASI A sensory score at 24 wks; modified Frankel scale at 24 wks

Hepatocyte Growth Factor Hepatocyte growth factor (HGF) is a c-Met receptor ligand that promotes angiogenesis, mitogenesis, and cell motility in the liver. In models of myocardial infarction and stroke, HGF has been shown to enhance angiogenesis and improve endogenous cell survival.84,85 In a preclinical study of SCI in non-human primates, intrathecal HGF was found to enhance ventral motor neuron survival, reduce cavitation at the injury epicenter, and improve motor outcomes.85 In a subsequent non-human primate study, HGF was shown to promote angiogenesis after cervical injury resulting in significant improvements in upper limb recovery.84 Kringle Pharma Inc. is now recruiting for a phase I/II placebo-controlled study (N = 48; NCT02193334) of KP-100IT (intrathecal HGF) in patients with modified Frankel scale A/B1/B2 cervical injuries within 72 hours of injury; 24-week follow-up results are expected in 2019.

[lunasicc42]

But the current eusol trial is about chronically injured patients correct? I wish I could find the results from phase 2 of this: https://clinicaltrials.gov/ct2/show/...draw=2&rank=49

[GRAMMY]

But the current eusol trial is about chronically injured patients correct? I wish I could find the results from phase 2 of this: https://clinicaltrials.gov/ct2/show/...draw=2&rank=49

A number of phase III randomized controlled trials(RCTs) testing the safety and efficacy of neuro-protectiveand regenerative therapies for acute traumatic SCI are currently underway (Table 3).


In a subsequent larger trial that involved 49 chronic SCI patients, application of aFGF with fibrin glue and duraplasty performed via laminectomy was combined with adjuvant booster treatment of combined aFGF and fibrin glue at 3 and 6 months post surgery via lumbar puncture. (179) Again, the use of aFGF was found to be safe and feasible; significant improvements were seen in ASIA motor and sensory scale scores, AIS grade, neurological level, and Functional Independence Measure (FIM) score at 24 months after treatment.

Reference (179) Wu JC, Huang WC, Chen YC, Tu TH, Tsai YA, Huang SF,et al:
Acidic fibroblast growth factor for repair of humanspinal cord injury: a clinical trial.
J Neurosurg Spine15:216–227, 2011 (60 patient trial and 49 patients completed the study)
LINK

Phase 1 LINK (9 patients)