Summit Therapeutics Share Discussion Threads

[hugus maximus] 27/2/2018 17:29

It would be good for moral to see a little positive anecdotal stuff luminoso .. but not sure where we'd see anything? Am I right in thinking that as the trial is open, anecdotal observation doesn't break protocol?

[luminoso] 27/2/2018 14:59

Has there been any comment from DMD parent/support groups on the 24 wk data ?

[chrisatrdg] 27/2/2018 12:15

Summit’s DMD drug cuts muscle inflammation in POC trial

[hugus maximus] 27/2/2018 10:46

I believe there is much myth and propaganda at play amongst NASDAQ shareholders about the science at work here and together with jingoism, somewhat naively many see the approach of gene therapy as the next quick fix for 100% of DMD population. As I know you've mentioned before Waterloo, the actual complexity and as yet much uncharted water involving gene therapy, is not going to be relevant if Summit follow ongoing success all the way down to final 48 wk data.

Something that may also set the cat amongst the pigeons is if Sarepta's Eteplirsen is turned down by the EU health body ... a decision is expected any day.

[waterloo01] 27/2/2018 09:25

One to one meetings today and SRPT update Thursday. Might get some indication of their interest. Might they make a move?

Reaction disappointing as I see it as another piece of evidence that Utrophin upregulation seems to be working.

[football] 27/2/2018 08:19

Maybe we should start releasing RNS's when the American market is open as every time we get good news and the share price rises on it soon as the NASDAQ opens they sell for a quick profit and we are back to square one.

[waterloo01] 26/2/2018 15:57

Summit Therapeutics has posted further data from the ongoing phase 2 trial of ezutromid. The latest analysis links the utrophin modulator to a statistically significant decline in muscle inflammation in boys with Duchenne muscular dystrophy (DMD).

Oxford, U.K.-based Summit generated the data on muscle inflammation by measuring MRI transverse relaxation time T2 (MRS-T2). The technique quantifies the breakdown and inflammation of muscle, making it a useful tool for assessing the progression of DMD. MRS-T2 values rise as DMD progresses but can be brought down by steroids.

The Summit data suggest ezutromid may drive reductions in MRS-T2 beyond those achieved by the use of steroids alone. All 38 participants in the proof-of-concept trial were on stable steroid regimes. After 24 weeks of twice-daily ezutromid doses, MRS-T2 decreased by 0.861 milliseconds, on average.

Summit needs to do more work to show whether that finding and others generated to date have a meaningful effect on the lives of people with DMD. But some observers see the data gathered so far as a source of encouragement.

“The decrease in MRS-T2 seen in PhaseOut DMD is encouraging and suggests ezutromid is having a positive effect on muscle health,” H. Lee Sweeney, director of the Myology Institute at the University of Florida, said in a statement. “These data could be an early indication that these patients are experiencing a decrease in disease severity and highlight ezutromid's potential as a disease modifying treatment.”

RELEASE: Summit Therapeutics unveils encouraging early data for Duchenne drug

Publication of the data on MRS-T2 comes a month after Summit shared a look at other endpoints. That earlier data drop linked ezutromid to a decline in muscle damage and an uptick in utrophin protein intensity levels. Together with the muscle inflammation readout, the data form the backbone of early efforts to show ezutromid is a disease-modifying therapy suited for use by all DMD patients.

Summit is short of making that argument conclusively. The next step is to post data from the full 48-week trial. Beyond that, Summit plans to move ezutromid into a pivotal study.

The progress of those studies will be closely watched by the DMD community and Sarepta, which celebrated the approval of its drug targeting the disease by striking a deal with Summit. Sarepta paid $40 million upfront and committed to more than $500 million in milestones to secure the rights to ezutromid in Europe and some other markets.

[algernon2] 26/2/2018 15:02

Singh said:

“We recently spent time with Summit (SMMT) management meeting potential investors and reviewing the recent positive 24-week results from ezutromid in PhaseOUT DMD and the upcoming Phase 3 pivotal clinical trial initiations for ridinilazole in Clostridium difficile infection (CDI). Uniformly the meetings started with a certain degree of skepticism regarding drug development in Duchenne muscular dystrophy (DMD), and ended with engaged interest in the ezutromid development program and the potential for ridinilazole in CDI. Perhaps what stuck out most to us was that investors cautiously agreed with our thesis that the DMD development space is worthy of investment and that ridinilazole in CDI is a free option at the current SMMT share price. We reiterate our bullish stance on SMMT.”

[waterloo01] 26/2/2018 14:21

Well I take that as a big positive in having a 3rd statistically significant measure, along side the MRI's and biopsy data to show that Utrophin upregulation is having an actual effect. All 3 are independent measures and I suspect would rate exceptionally well against the SRPT data that got approval. I'm not sure however that's that's clear in the RNS (maybe there will be a proactive type interview to add some flesh?)

It would seem that it's not the quantity of Utrophin that matters, but again some more granular data (which they must be working on) might show a correlation with utrophin levels and muscle repair.

Hopefully more will come out pre 48wk data.

[chrisatrdg] 26/2/2018 13:41

Good RNS & good comments from everyone glad freedosh to see your posting today & your positivity.

Will be interesting to see if the NASDAQ responds as well as AIM is at the moment.

[luminoso] 26/2/2018 13:19

England were on vallium IMO ! Fair play to the Scottish team, though. Great tries.

[freedosh] 26/2/2018 13:01

Indeed but it was clearly Scotland that were in the active Ezutromid arm. England on placebo!
For full disclosure purposes: I'm a Scot.

[hugus maximus] 26/2/2018 12:50

Owen Farrell .. top bloke.

[hugus maximus] 26/2/2018 12:49

sorry crossed posts ... indeed ... let's hope England have a serious conflab .. they've been doing so well.

[hugus maximus] 26/2/2018 12:47

A very sad comparison Freedosh! The Scots simply went to work and cracked them. More importantly ... do you think latest RNS here as significant as seems to a layman?

[freedosh] 26/2/2018 12:47

We are on a home run now.

[freedosh] 26/2/2018 12:42

Indeed Hugus. A reasonable comparison would be Scotland vs England,IMHO.
Ho ho

[hugus maximus] 26/2/2018 12:16

Calf muscle surely a pivotal piece of data?

[hugus maximus] 26/2/2018 12:15

Is 31.850 milliseconds to 30.989 milliseconds, 95% CI, -1.440, -0.281 a strong enough stat to suggest it's actually halting deterioration?

[hugus maximus] 26/2/2018 12:14

Indeed ... this looks convincing.

[waterloo01] 26/2/2018 12:09

Backs up using this as an endpoint.

[hugus maximus] 26/2/2018 12:03

RNS ... looks good

SUMMIT ANNOUNCES NEW ANALYSIS SHOWING EZUTROMID SIGNIFICANTLY REDUCED MUSCLE INFLAMMATION IN PHASE 2 CLINICAL TRIAL IN DMD
MRS-T2 Data Provide Evidence of Early Impact of Ezutromid on Downstream Muscle Health
Data Build on Positive Biopsy Findings that Showed Significant Decrease in Muscle Damage

Oxford, UK, 26 February 2018 - Summit Therapeutics plc (NASDAQ:SMMT, AIM:SUMM) announces further positive findings from PhaseOut DMD, a Phase 2 open-label, multi-centre clinical trial of the utrophin modulator ezutromid in Duchenne muscular dystrophy ('DMD'). Further analysis of the 24-week interim dataset showed a statistically significant decrease in muscle inflammation as measured by magnetic resonance spectroscopy transverse relaxation time T2 ('MRS-T2').

"MRS-T2 is an objective technique used to monitor DMD disease progression as it allows for the precise quantification of changes in muscle breakdown and inflammation. MRS-T2 values typically increase over time in DMD," commented Dr H Lee Sweeney, Director of the Myology Institute at the University of Florida and Co-Director of Imaging DMD. "The decrease in MRS-T2 seen in PhaseOut DMD is encouraging and suggests ezutromid is having a positive effect on muscle health. These data could be an early indication that these patients are experiencing a decrease in disease severity and highlight ezutromid's potential as a disease modifying treatment. I look forward to seeing further findings from PhaseOut DMD."

The reduction in MRS-T2 measured in PhaseOut DMD is consistent with the expected activity of ezutromid to stabilise muscle fibre membranes and thereby reduce muscle fibre damage and inflammation. A statistically significant and meaningful reduction in muscle fibre damage was observed in previously reported 24-week findings from patient biopsies in PhaseOut DMD.

Published research has shown reductions in MRS-T2 in DMD patients treated with steroids.[1] All patients in PhaseOut DMD have been on stable steroid regimens and therefore the MRS-T2 reductions observed are in addition to any anti-inflammatory effect provided by steroids.

The new MRS data showed a statistically significant decrease from baseline in the T2-relaxation time in the soleus (calf muscle) in patients (n=38) treated with ezutromid. The mean decrease was -0.861 milliseconds from baseline to 24 weeks (31.850 milliseconds to 30.989 milliseconds, 95% CI, -1.440, -0.281). The soleus is one of the most reliable leg muscles for monitoring disease progression via T2 relaxation time in DMD with increases shown to correlate to loss of functional ability.[1,2] Published natural history data show that T2 relaxation times increase with disease progression due to the relentless cycle of muscle damage and repair leading to inflammation.[1,2] A mean decrease of -0.470 milliseconds in MRS-T2 was also observed in the vastus lateralis (thigh muscle) in ezutromid-treated patients (n=37) from baseline to 24 weeks (32.265 milliseconds to 31.795 milliseconds, 95% CI, -1.158, 0.218).

"The 24-week interim analysis has shown encouraging signs of ezutromid activity in PhaseOut DMD. These MRS-T2 findings show a positive impact on downstream muscle health," added Dr David Roblin, Chief Medical Officer and President of R&D at Summit. "This, combined with the evidence that ezutromid can modulate production of utrophin protein and significantly reduce muscle damage, is further evidence of the potential of ezutromid as a disease modifying approach for the treatment of all genetic forms of DMD."

[chrisatrdg] 23/2/2018 21:44

Key events next week - healthcare - mentions Summit but also Sarepta Thursday (3/1): Sarepta Therapeutics (NASDAQ:SRPT): Q4 results (premarket).