Searching for a cure, Improving lives

Conference 2016 Company Q&A Sessions

Friday 11 November

Workshop One Rooms 1-6 2nd floor


Capricor Therapeutics – Deborah Ascheim

Q:  How do you envisage ‘HOPE’ working alongside other potential treatments and therapies, for example Ataluren and steroids, is this part of the trial?

A:  Yes, they have considered this.  Capricor Therapeutics hold the view that there is not going to be a ‘magic bullet’, so many mechanisms contribute, it will be administered in conjunction. Stem cells are not from skeletal muscle but from the heart.  A very tenacious Mum brought this compound to their attention, she sat outside the office until they spoke to her, she had become aware of this compound working in patients after heart attack, working on scar tissue, and she urged Capricor to look into it to see if it could offer some benefit.  This was 7 years ago.

The HOPE project (Halt cardiomOPathy progression) CAP1002 is looking at Duchenne patients with left ventricular scarring in at least 4 cardiac sections.

Q:  What is the potential of exosomes in the treatment of Duchenne and what are your clinical trial plans to further develop this as a therapy?

A:  They have been looking at the Exosomes which are tiny vessels present in many proteins and perform different activities, the placenta for example is rich in making exosomes.  They mimic effectiveness of cells and are now looking beyond the heart.  Exosomes are tiny vessels and are not suitable for administration via the bloodstream, so are looking at modifying them.  Because of their physical nature, they are firstly looking at the eye and wanting to expand to the Duchenne platform.  They hope to include this in clinical trials.

Q:  Do you think there will be any associated adverse events or risks with the actual procedure?

A:  They are committed to the HOPE trial and looking at evaluating the cells, administering into the coronary arteries via catheter, threading to the three main arteries, using an angiogram to see the results.  This has not previously been done in children with DMD and there are different pathologies between a child and an adult.   Side effects can include bleeding under the skin at the access site, haematoma, bruising, slight headache and rash with a more serious risk of reaction to the dye including a risk of abnormal heart rhythm, heart attack or stroke, excessive bleeding.

This is an ongoing trial, so they cannot discuss the adverse side effects that have been seen in the trial as yet, but they can say that safety monitoring has allowed the trial to continue.

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Summit Therapeutics – Michelle Avery

Q:  Provided that the results of the ongoing clinical trial phase 2b of Ezutromid are positive, are you planning to involve even younger patients e.g. 2-4 years old in the next phases?

A:  Currently the trial participants are aged 5-10 years old. In this trial, Summit are testing a utrophin modulator, which seeks to change the expression of utrophin and potentially substitute for dystrophin in mature muscles. Summit are looking at measures for Utrophin, muscle maturity and regeneration, MRI, functional measures like 6 Minute Walk Test (6MWT) and North Star Ambulatory Assessment (NSAA) and also monitoring the heart and lungs. Summit expect a whole host of data to come out of the trial, which will help to inform future clinical trials and may allow them to look at different age ranges in the future.

Q:  Provided that the results of the ongoing clinical trial phase 2b of Ezutromid are positive, would you consider filing an application for approval to the regulatory authorities immediately after completing that phase?

A:  Expect to start seeing ‘hints’ that it is working as predicted and safe in the PhaseOut DMD trial.  If the data are positive, Summit believe they would need to run an additional trial aimed at receiving regulatory approval.

Q:   If initial data from the PhaseOut DMD study shows a positive result will there be a continuous seamless extension from 48 to 96 weeks?

A:  PhaseOut DMD is a 48 week trial with the potential for an extension period. The decision to extend the trial will be based on safety data from PhaseOut DMD. Summit’s intention is to make this decision with sufficient time to amend the protocol and allow the first patients who complete the initial 48 weeks of treatment to have a seamless transition to the extension phase, but this will depend on the Regulators. In PhaseOut DMD, Summit are looking at two different formulations of ezutromid to test the safety and efficacy of a wide exposure range. Summit expects that patients in the extension phase would continue on whichever formulation they began the trial until there are data that would support one formulation over the other, at which point, they would expect to switch patients onto the formulation deemed to have a better safety and efficacy profile. Again, this would depend on the Regulators.


WAVE Life Sciences – Wendy Erler

Q:  How would you describe your antisense oligonucleotides? What chemistry, and how are they different?

A:  WAVE is developing a single pure drug. Nucleic acid therapeutics are poised to radically change the medical landscape, offering the potential to treat numerous serious, often devastating, genetically defined diseases including DMD.

To date, nucleic acid therapeutics have been comprised of complex mixtures of hundreds of thousands of chemical entities known as stereoisomers. Some stereoisomers in these mixtures have therapeutic effects, while others are less beneficial or contribute to undesirable side effects. Uncontrolled stereoisomer drug mixtures can lead to suboptimal efficacy and increased risk and safety concerns.

WAVE’s novel chemistry platform eliminates these complex chemical mixtures, giving them control over the pharmacology of their stereopure medicines in development. Rationally designed, WAVE’s stereopure nucleic acid therapies precisely target underlying disease biology and in their proof-of-concept studies they have demonstrated improved activity, stability, specificity and immunogenicity compared with stereoisomer mixtures. As a result, WAVE believe they will be able to maximize therapeutic effect while minimizing the potential for side effects and safety risks.

Q:  What are your future global clinical trial plans?

A:  WAVE is a small company and still in the preclinical phase.  WAVE intends to begin Phase 1 in the clinic, expected at the end of 2017.

Q:  For the second generation exon skipping platform, do you feel this will be more effective than the current generation?

A: WAVE has shown preclinical data that shows increased skipping efficiency and dystrophin production compared to current exon 51 therapies that have been studied.

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Tivorsan Pharmaceuticals – Justin Fallon

Q:  What is the difference/benefit of Biglycan over other utrophin up-regulators?

A:  They ask how does the body deal with Utrophin and Biglycan and can this help the muscle function. They can produce a quality and quantity and are very enthusiastic about next stage.

Utrophin takes the place of dystrophin, they ask how does the body deal with Utrophin and can Biglycan help the muscle function. The body normally regulates Biglycan. Their task was to produce this is in sufficient quality and quantity and have now achieved this and are very enthusiastic.

Q:  What are your clinical trial plans for this potential treatment and timelines?

A:  They are on track to start clinical trials next year and are currently at the end of the preclinical stage.

Q:  What is the potential of this treatment to be given in combination with other targets of DAPC? (Discriminant Analysis of Principal Components)

A:  In combination potentially with exon skipping, but not all areas.  Headroom for Utrophin in all fibres and Biglycan will be complimentary.  Biglycan is likely to bring utrophin to the membrane.


Bamboo Therapeutics – Sharon Hesterlee

Q:  According to the information on your website you anticipated commencing the clinical trial in the second half of 2017.  Where will this trial take place (US and/or Europe)?

A:  Trial sites have not yet been identified, but will likely be in the US for the phase I/II study.  Bamboo will announce where the trial sites will be when they have IRB approval for the trial.  The trial is currently planned to start in the second half of 2017, subject to the outcome of their remaining preclinical studies.

Q:  Can you tell us about your gene therapy product?

A:  Bamboo are delivering a miniaturized version of the dystrophin gene, called a “mini-dystrophin gene,” inside a viral particle that is based on the adeno-associated virus, serotype 9—or “AAV9.”  AAV is one of the smallest viruses known and doesn’t normally cause symptoms in humans; however its small size means that a miniature version of the dystrophin gene is required for it to physically fit inside the viral particle.  Together, the mini-dystrophin gene and the viral shell are known as a “vector.” In studies of animals that lack dystrophin the vector has been able to deliver the mini-dystrophin gene to muscle cells where it is used to make a mini-dystrophin protein.  They have seen evidence in these animals that the mini-dystrophin can, to some extent, correct symptoms caused by the lack of dystrophin.  In the clinical trial, Bamboo currently plan to deliver their vector systemically by an intravenous injection.

Q:  What are your objectives with your relationship with Pfizer?

A:  By becoming part of Pfizer, Bamboo hope to be able to scale up manufacturing of the clinical grade vector to amounts that will be required for an approved drug.  They also gain tremendous general expertise and resources that are not typically available to a small biotechnology company.  Finally, because Pfizer has an active focus on gene therapy and has experience in developing therapeutics for Duchenne, there are many synergies within the company that may benefit the Duchenne gene therapy programme.

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Bristol Myers-Squibb – Andrew Napoli

Q: What are your future clinical trial plans in Europe and have you had meaningful interaction with the regulators?

A: They have had a meaningful, productive and constructive interaction with the Regulators. A global study is scheduled for the first half of next year, which they expect will include sites in Europe.


EspeRare – Florence Porte

Q:  What is Rimeporide and can you tell us where this fits in the Duchenne pipeline?

A:  Rimeporide is a potent and selective inhibitor of the sodium/proton exchanger. Its activity modulates the damaging ion imbalances that are associated with the deterioration of function of dystrophic muscle especially Calcium, Sodium and pH. Rimeporide prevents calcium related necrosis and sodium related oedema in cardiac and skeletal muscle and through its action of ion balance homeostasis, it is anticipated that treatment with rimeporide will be muscle-sparing and may alleviate long-term accumulated muscle and myocardial damage and inflammation, particularly if treatment is initiated early in disease progression. Its unique ability to prevent cardiomyopathy as well as the decline in muscle function, with no restriction on age and on genetic subtypes, makes it an important complement to other treatments that restore or augment dystrophin.

Q:  What are your clinical plans for this compound and have you had interaction with the regulators?

A:  EspeRare is currently leading a multicentre European clinical phase Ib study in young patients with DMD, 6 to 14 years old. Currently four sites are open for recruitment, one with Pr Muntoni at the GOSH, one with Dr Gidaro and Servais in Paris at the I-Motion Centre, one with Dr Diaz in Barcelona (Santa Creu Santa Pau) and one site with Dr Previtali at San Raffaele in Milano.

The objective of the study is to establish the safety and tolerability of rimeporide in young children, to characterize the pharmacokinetic profile and to explore pharmacodynamic endpoints including MRI endpoints and serum biomarkers monitoring inflammation and fibrosis.

The end of the recruitment will be closed by second quarter 2017.

In June 2015, EspeRare went to the EMA for scientific advice with the CHMP. The first objective was to get approval about the design of the ongoing phase Ib study and also to get preliminary advice on the design of further pivotal clinical study(ies).

They also discussed the biomarkers strategy.

Based on this preliminary advice, it looks that a single pivotal clinical trial could support conditional approval in EU.

Next year will be dedicated to completing the phase Ib study, to look for a partner to launch the pivotal

programme as they believe that a mid-size to large pharma company having the adequate infrastructure to launch the clinical study will be more efficient.

EspeRare would like to start working on the design of the pivotal study with their partner ASAP in order to have a new phase II.III study launched in 2018.

Q:  What other drugs are you working on for Duchenne?

A:  Started this summer to reposition a second project in DMD in collaboration with Prof. Dominic Wells in MDX mice. The preclinical programme is funded by Duchenne UK. Results will be available by 2nd quarter 2017.

This new project was initially developed as an antifibrotic compound and showed benefit in several animal models of lung/kidney fibrosis where it was able to consistently and dose dependently decrease the release of TNFa, the recruitment of lymphocytes, neutrophils and macrophages in a statistically significant manner. It also consistently and dose dependently reduced the fibrotic area, the collagen deposition and production as well as the TGFb release in a clinically significant manner. These improvements in the level of fibrosis are thought to preserve muscle function and delay the progression of the disease in patients with DMD. This compound was also shown to be safe in human adults for a treatment up to 5 months.

Recent literature articles point to positive effect of the inhibition of this pathway in DMD to prevent inflammation and fibrosis.

EspeRare are also testing a combination between Rimeporide and this new compound to look for a synergistic effect as both compounds act on different fibrosis and inflammation pathways.


Solid Biosciences – Carl Morris

Q:  I heard recently about your gene therapy programme, what are your plans in developing this?

A:  AAV microdystrophin programme is in pre-clinical development. Manufacturing is a big issue and is time consuming, so this is what they are focusing on currently.  They are going through the standard drug process, looking at functional benefit, toxicology study, getting a package together for the FDA.

Q:  A recent community update told us about other work you are doing in Duchenne, can you give more information?

A:  They have expanded the pipeline, the LTPB4 programme seems to modulate probiotic factor and inhibit the release of TGF(beta). A second programme, similar to galectin-9 will bind to the external part of the muscle, stabilise from the outside in the absence of dystrophin on the inside.

Statins show benefit in the MDX mice, so they are doing further work, looking at biomarkers, to see if there is value in advancing that. They also have a Solid ‘suit’, an assisted device to assist the declining function of the body.

Q:  What plans do you have for clinical trials next year?

A:  Hopefully next year, they will evaluate the outcomes of other research.

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Santhera Pharmaceuticals – Jodi Wolff

Q:  Can you tell us more about your recent regulatory updates and potential timelines for approval?

A:  In June 2016 the EMA validated Santhera’s submission for Raxone to treat DMD thereby confirming that the submission is complete and the review process for the CHMP has begun.  They expect to receive a response from regulatory authorities in the first quarter of 2017.  The process is going smoothly.  The intended indication for Raxone initially is boys with DMD who are not on steroids and are experiencing respiratory decline.  The basis for Santhera’s application is the DELOS positive Phase III trial indicating that there is an anticipated benefit for boys experiencing respiratory decline but who are not currently using steroids (even if they have previously used steroids).  Santhera’s ongoing SIDEROS trial in boys using steroids is designed to evaluate whether Raxone could benefit a wider group of boys experiencing respiratory decline.

Q:  Can you describe the SIDEROS trial, the design and global plans?

A:  SIDEROS is a Phase III, placebo controlled trial in a large cohort of 260 boys on steroids. Participants will be randomised 1:1, half taking 900 mg of Raxone daily (2 tabs x 3 times a day with food), half taking a placebo, for boys of 10 years and over at 64 centres in US and Europe.  Patients need to have between 30% and 80% Forced Vital Capacity (FVC).  The boys are expected to have declining respiratory function already.  Patients completing the trial after 78 weeks will be offered open-label extension indefinitely until we get marketing authorisation or discontinue the programme. The study has started to enroll patients in the US and Belgium; the four UK sites will be expected to begin enrolling early 2017

Q:  How would you describe the additive benefit of this drug in comparison to steroids?

A: This drug is not meant to be a replacement to steroids.

In Santhera’s research using the CINRG natural history database, they have found that steroids can delay the start of respiratory function loss on average, by about 2 years. This is similar to what is seen with delaying the loss of ambulation in steroid vs. non-steroid using boys. For example, instead of the start of the decline at 10 years old, it is delayed until 12 years.  However, once a decline to 80% of normal function is observed, decline continues in the same way at the same rate regardless of steroid use. This suggests that steroids don’t affect the rate of decline of respiratory function.

The positive phase 3 DELOS trial suggests Santhera can reduce the rate of respiratory function decline with idebenone in boys not using steroids. Their SIDEROS trial will help them identify if, and how much benefit idebenone could achieve in boys using steroids.


Questions from the floor

To whole panel, how many have been to EMA scientific advice protocol?

[BMS] We have received feedback on overall clinical programme and endpoints within the study design.

[Esperare] have had 2 separate meetings for strategy advice and endorsement of clinical plans.  They have discussed the weaknesses of the 6MWT – this was a very constructive meeting.

[Capricor] are planning a meeting with the EMA in the future

[Santhera] have talked to them a lot about clinical trial design and natural history

[Summit] can’t comment specifically on their interaction with the Regulators but they value their interaction.

[Tivorsan] have interacted with the FDA, and were advised what to do and they have done it.

[Solid] yes

[EspeRare, Tivorsan] went to TACT and are willing to share what they have done

[Wave] We plan to conduct a TACT review if possible.

Regarding the 2 gene therapy programmes, what are the challenges to administering the virus?

[Solid] If they inject a viral vector the recipient is likely to develop antibodies, therefore are unable to administer it again. If they provide an infected dose, there will be no benefit because of immunity. They are still trying to assess where they see immunity, risk to safety, and are assessing optimal dose.

[Bamboo] are aware of this too.

To Wendy, exon 51 skipping trial to start next year?

Our intention is to include both Non-ambulant boys and ambulant patients in our studies and begin at the end of next year. However, the trial design is not finalised yet and assessment points are not yet finalised.

To Michelle, how long does the Regulator take to decide?

Sooner rather than later.  We have plans to go to the Regulator for approval before the 48 week point.

To the panel, can you tell us about the outcomes and biomarkers?

[Summit] for the current trial, we are developing a biomarker for muscle biopsies, which could be used with other therapies. The biomarkers are designed to assess muscle maturity and regeneration. They hope to be able to share this with other companies.

They are looking at MRI as non-invasive measure, but don’t know if the Regulator will accept this for a registration trial.

[EspeRare] drugs not acting directly on dystrophin but on the downstream effect of the lack of dystrophin.  They are aware of the weaknesses of the 6MWT.

Agreement to accept co-primary endpoints? They may be able to capture by MRI, the Regulator may accept this.

How to capture quality of life? Digital tools have been developed to capture activities at home etc.  There is a lot of work to be done here, will help to get fair prices for these drugs.

[Capricor] MRI, other parameters for more subtle effects, they don’t know if these are significant yet.

Also looking at parameter to measure quality of life and skeletal muscle.

Passive data collection devices to record more subtle outcomes.

[Bamboo] When you do see a change in a clinical trial, how significant is that, what does that difference mean? We are collecting natural history, observational recordings.

[Summit] must currently exclude patients on disease-modifying trials. Many people think combination therapies are the future but they need to show it is effective on its own first.

For a current trial, potential participants need to wash out of an experimental trial for three months first, then they can go on a different trial.

[Solid] Clinical study is an experiment, if it is effective and gets approval, taking on or off is hypothetical, but they want to do the best for the boy.  They could look at combination, if they compliment each other, that is the hope.

To the panel, Sibling protocol – would you consider?

[Solid] have to make sure the drug works, so need a careful, comprehensive trial design, consideration of siblings would be in their plans.

Gene therapy, significant manufacturing hurdle that we need to overcome.

[Wave] hard to make Duchenne drugs, they have talked about a compassionate use programme, but this is so far in the future for us. Sibling protocol, entry has to be so tightly defined for dosing requirements.

[Summit] not yet got a compassionate use or sibling programme, but will continue to evaluate this.

[Santhera] has not yet got a sibling programme.  They have been talking about compassionate use but nothing has been decided.

[BMS] We are looking to establish efficacy and safety before considering compassionate use.  

[Bamboo] are preclinical so not relevant yet.

[Capricor] exploring on a policy level currently.  They are small, so in terms of access, it will be tough to do a compassionate use programme but a sibling programme is a modified compassionate programme.

[EsperRare] Nothing to add, it is too early for them to consider a compassionate use programme.

Quality of life measures

[BMS] plan to include disease specific and generic quality of life measures in our next trial, and also evaluating measures of caregiver burden

[Bamboo] have had trouble finding quality of life measures that are sensitive enough in Duchenne

[Summit] are including PODCI (Pediatric Outcomes Data Collection Instrument) and working with patient groups in Europe and the US to get measures of quality of life.  Different measures mean different things to different families.

[Wave] it is too early but would welcome input.

Patient input into trial protocol

[Wave]  We are committed to patient input every step of the way.

[Solid] it is a core part of their mission to bring in the patient

[Bamboo] are planning patient-centric clinical trials. They are trying to understand what parents go through when their child is on a trial.

[Santhera] has submitted a patient preference study to the FDA, working with patient groups

[Summit] are meeting patient organisations in Europe and the US and expect to get feedback on trial logistics etc.

[BMS] We have sought patient advocacy and individual patient input into trial designs.  We are also trying to learn from our ongoing study so future trials are easier for patients and caregivers.

[Capricor] have worked with a number of parents, founders of different advocacy groups, and this has been invaluable. They are developing a process to bring in more patients at an early stage.

What are the biggest challenges with trials? Is it harder to find patients to recruit for trials, or the funding?

[Esperare] are struggling to find money but have patients.

[Capricor] are a small biotech company, it is challenging to fund trials. They have enrolled more rapidly than they thought they would.

[Bamboo] It is a challenge to use endpoints more effectively to recruit a wider population.  The classic cohort is 8-12 year olds, ambulatory, but this isn’t the whole population.

[Bamboo] trial sites are limited, therefore are limited to those boys who can go to the trial centre and who have a physician recruiting for trial.  They need to work with the physicians to expand trial sites.

[Tivorsan] are are a small company so funding and patient availability are both problems. They are investigating recruiting later so they are not restricted to the cohort currently used.

[Wave] need to reach out to families who don’t come to meetings like this, who don’t ask their doctors what trials are available.

From the floor: “For parents in the UK, it is very tough to access trials.  Our local hospital is not a trial site so we have to travel a huge distance”

[Wave] the pharmas are aware of this, they support Action Duchenne in developing satellite centres to increase recruitment on to trials.


Saturday 12 November

Workshop One Rooms 1-6 2nd floor


Italfarmaco – Paolo Bettica

Q:  I’m not familiar with your potential treatment can you describe a bit more about the target?

  •    Givinostat – HDX inhibitors, anti-inflammatory, inhibition of fibrosis.  They are aiming to counteract damage in the muscle, replicating the MDX results in ambulatory children with DMD. HDX are over produced, which is where Givinostat plays a key role as an anti-inflammatory drug. It is an active inhibitor of fibrosis.
  •    Givinostat works against muscle damage and replaces the fat in muscle
  •    They have replicated findings in 20 ambulant children. After taking muscle biopsies after 1 year of treatment, there was reduced fibrosis and fat replacement.
  •    Givinostat is an oral suspension, 2 x doses delivered daily
  •    It has been tested in different diseases, ie all the toxicology has been completed

Q:  What are your clinical trial plans in Europe over the next year?

  •    Study 43 is continuing. In 4th year of treatments for 20 children on Givinostat
  •    They are starting a pivotal trial, double blind placebo study in children aged 6 years and over who are ambulant and on steroids. The trial will run for 18 months with 2:1 randomised control (2 children take the drug, 1 take placebo) in US and Europe
  •    They are measuring MRI in all children, at the baseline and at 4 months. Their primary objective is the 4 step climb.

Q:  Do you have any updates from the regulators?

  •       Givinostat has received fast track designation from EMA and FDA
  •       Study 48 is with EMA
  •       Received clearance from FDA for study in US


Pfizer – Michael Binks

Q:  What is the goal of anti-myostatin in potentially treating Duchenne?

  •       Currently in Phase II study
  •       There are clinical benefits, gaining confidence around the myostatin biology, common phenotype knock-out, similar muscle growth.
  •       Critically important medication in muscle biology
  •       When they removed the myostatin in the MDX mouse, they found increased strength and reduced muscle inflammation and fibrosis
  •       For people living with Duchenne who are treated with Domagrozumab, we hope that this will translate into a clinical benefit for them that 1) there is an increase in strength 2) inflammation is reduced 3) there is an improvement in performance measures, such as the ability to climb stairs and walking.
  •       In extending or delaying fibrosis and inflammation, it is expected that there are delays to motor loss and delays to loss of function.

Q:  How is your study going, when can we expect to hear the first results?

  •       Phase 2 is a pivotal study, they have agreed with the global regulators that if they should meet the milestones and endpoints, they will satisfy the regulatory requirements.
  •       This is a large and long study.
  •       If there is a positive outcome, approval should follow shortly
  •       They have had difficulty recruiting as the trial lasts for a 2 year period. They are ¾ of the way through recruitment, still have 25 boys to recruit. The first boy has completed his 2 years on they study. 23 boys have completed 1 year on study. No serious adverse effects/events. 2 boys withdrawn from study due to minor reaction to the protein injection.
  •       Data is reviewed monthly

Q:  I heard about the inclusion criteria recently changing, can you give us a bit more information?

  •       It is necessary to make changes to the protocol every now and again, particularly on long studies.
  •       The 2nd protocol amendment was to extend the age range. Previously the limit was 6-10, now they have taken off the upper limit.
  •       The previous limit of 10 restricted the set of natural data, it is important that they have good availability of a broad range of data.  The endpoint is the stair climb, so in retrospect, it was not necessary to cap the age at 10 years old. They can recruit older boys and not see too much variability in the endpoint.
  •       There have been minor changes such as removal of minor tests and reworded the study etc, to use at 2 year point.

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Akashi Therapeutics – Diana Escolar

Q:  Can you tell us what is happening with HT-100 and the clinical hold? What are the next steps if the FDA recommend to discontinue or if to proceed?

  •       HT-100 is on hold since January 2016. They have continued to follow the children and collect the data while the children are off the drug.
  •       There is a discussion in December with the FDA and they are hopeful there is a way forward. They are providing an extensive document with results.
  •       They are confident in their platform, and that there is efficacy in low doses where there are no risks. Restoring dosing safely will be the next step.

Q:  What other potential compounds are you developing?

  •       There are 2 other compounds being developed

1)   DT-200 , a selective androgen receptor modulator (SARM) which is a non-steroidal muscle builder, which also decreases muscle necrosis. Studies in the MDX mouse have shown this could be a treatment for DMD. They know its safety profile, as the drug has been tested in 70 normal human volunteers. These types of drugs are also being developed for older people with muscle atrophy, but DT-200 is 5 times more selective for muscle which allows an increase in dose to have better effect in muscle without the off target side effects. The next step is a proof of concept study in the UK  in the first quarter of 2017, testing the effect of three dosages in increasing muscle mass and motor function in normal human volunteers.

2)   AT-300 is a stretch activated calcium channel modulator (remains open in muscle membrane) that helps the calcium channel to close properly. Currently at the preclinical stage, with positive effect in the MDX mouse.  IND enabling studies are planned for 2017, with filing to FDA for first in human studies Q4 2017.

Q:  What are your future clinical trial plans outside the US?

  •    DT-200 Phase 1 in UK
  •    HT-100 pivotal trial will be international
  •    AT-300 proof of concept in US then internationally


Catabasis – Joanne Donovan

Q:  Provided that the results of the ongoing clinical trial MoveDMD phase 2 of Edasalonexent are positive, would you consider filing an application for approval to the regulatory authorities immediately after completing that phase?

  • Currently gaining information from the MoveDMD Phase 2, a 12 week placebo controlled study with edasalonexent, which targets the NF-kappaB protein that is central to progression in Duchenne.  Anticipate a positive effect on delaying progression of Duchenne, with an MRI as primary endpoint.
  • An open-label extension up to 48 weeks is ongoing.
  • The trial is enrolling 4-7 year olds not on steroids for at least 6 months.  Also looking at 4 step climb, time to stand, 10 metre walk/run, all of which are appropriate for this age.
  • MoveDMD is a relatively small study, which is possible as MRI is less variable, and doesn’t depend on the boys’ performance on that particular day.
  • If the trial is positive, plan to move to Phase 3, pivotal study in the second half of 2017 as quickly as possible because of the urgency.

Q:  How do you see the new generation of steroid replacement therapies and what advice would you give a new parent who is considering this versus current steroids?

  •       NF-KappaB is a target of steroids. However, steroids have significant side effects, including osteoporosis, fractures, and muscle atrophy in other settings. Overall the balance is positive in Duchenne, and the hope is to develop edasalonexent to have a better balance of benefit to side effects.  
  •     Catabasis’ hope is that the compound would be used as a foundational therapy, instead of steroids. It may have a similar, if not greater effect, with the potential for muscle regeneration.
  •       An NF-KappaB inhibitor could be used without steroids, alongside other treatments, as a disease modifier.

Q:  What are your future plans for Europe for clinical trials and also the potential of this therapy in non-ambulatory young people?

  •       Phase 3 for 4-7 year olds not yet on steroids is being planned as a global study. We are working on identifying sites.
  •       Planning non-ambulatory study in 2nd half of 2017 since a significant number of boys stop steroids after they lose ambulation.

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Sarepta Therapeutics – Edward Kaye

Q:  What commitment is there to work on rarer Exons?

  •    Looking forward (2 years) the primary focus for the company is Duchenne.
  •    Opening up studies in 2017 for Europe and beyond for 45 & 53.
  •    We have an additional 3 drugs at preclinical stage
  •    7 drugs at selection stage
  •    They are working with the regulatory authorities to find a regulatory pathway for the following exons, using the same class and backbone technology, there has to be a more efficient way for rarer exons.
  •    They are considering how much pre-clinical work will be needed, and are using dystrophin as an endpoint.
  •    The regulatory authorities are waiting to see their results.
  •    Europe reviewing Eteplirsen, then 45 & 53 and working on pathways

Q:  Is there a strategy to approach regulators (FDA and EMA) to speed up approval of formulas for rarer Exons if effectiveness is proven for the common Exons?

  •    Yes, there is a joint meeting with the FDA and EMA, with discussions between the agencies

Q:  Whilst the community is delighted about the approval for ExonDys, how would you respond to claims by others in the healthcare field that the data wasn’t sufficient and there was an overemphasis on lobbying?

  •       There was conflict within the FDA about whether they have enough to get approval.
  •       The Division of Neurology had never done accelerated approval.  Disagreements were aired but the FDA can only approve on the basis of data.
  •       Patient-reported outcomes were reported, but the FDA doesn’t respond to political pressure.

Q:  Our 19 year old daughter (Born January 1997) was diagnosed as A Manifesting Carrier of Duchenne Muscular Dystrophy in early 2008. She has a deletion (one copy) of Exon 42-43.

She is still very ambulant, but uses her wheelchair or ‘buggy’ occasionally. She was also born with three VSD’s (now fully repaired) and scoliosis which does affect her posture.

Our question is, as a female,

(i)      when will she become eligible for the exon skipping research programme, to receive treatment, as it appears the emphasis generally is at the 48-51 range, messy genes and boys only ! and : (ii) what can be immediately done for her, to at least slow down, or even stop, her muscle wastage ?

  •    Women are not included as the number of symptomatic carriers is so small. Once the therapies are approved, the physician can use it ‘off-label’ and it should provide a similar benefit to that seen in boys and men. It would be up to the country or insurer to pay. Some other companies provide for male/female, not just male specific.
  •    [Pfizer] have prescribed to patients who were manifesting carriers, they didn’t restrict the label.
  •    [Akashi] treat manifesting carriers in the same way they treat the boys.  It is up to the manufacturers to agree that they will be treated, then it is up to the Regulators
  •    [PHASEBio] are trying to be inclusive, their therapy is applicable to anyone with cardiomyopathy.

Q:  Can you tell us more about“leaky gene” syndrome – this was put forward by Professor Sue Fletcher a few years ago, what is the current understanding?

  •       A ‘leaky gene’ was a gene modifier which affected the outcome. There are a certain number of mutations, boys amenable to exon skipping 46-57 who have an amount of dystrophin being released which allows them to walk longer etc.
  •       It is important that lots of genes are important, and it is not just the dystrophin gene that may be modified.


PHASEBio – John Lee

Q:  Can you tell us a bit more about the drug you are developing?

  •    They are a small, venture backed company near Pennsylvania.
  •    They attach scientific protein ‘tails’ to molecules, with Vasoactive Intestinal Peptide (VIP), which is a fusion protein.
  •    They are addressing cardiomyopathy and heart failure in Duchenne
  •    The technology mechanism increases the filling, pumping of the heart, increases the ability to vasodilate. It also shows pronounced anti-inflammatory effects.

Q:  What are your global clinical trial plans?

  •    At a high level, they have a global regulatory plan for Europe. There seems to be lots of motivation and many patients in Europe now who would take part.
  •    They are in Phase 2
  •    There are pressures of cost, but would open up sites for recruitment depending on financial details.

Q:  What design of trial are you considering?

  •    Phase 2a study to prove it is safe with multiple doses, as delivering multiple doses can prove problematic when people with Duchenne are likely to be on a substantial medication regime already
  •    Part 1 is in adult heart failure, not Duchenne, delivery of the medication weekly by subcutaneous injection, along with standard care meds.
  •    Part 2 is to target dose levels and assess safety and CMRI, decided to bring on Duchenne cardiomyopathy patients
  •    They will measure muscle functional and biomarkers from the data in a global multi-site study by middle of 2017.

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PTC Therapeutics – Stuart Peltz

Q:  Can you give us a further update on your recent regulatory meetings and next steps, are you confident for approval in the US and also the renewal of conditional approval in Europe?

  •    Translarna has continued to be marketable in Europe, the patients on the drug stay on the drug, with 90% compliance levels based on thorough review of results.
  •    The regulators have decided the benefits outweigh the risks.
  •    In US they received a refusal to file from the FDA Division of Neurology because the data missed the statistical significance
  •    They demonstrated clear benefit in the placebo trial, with all patients who were dosed with Translarna doing better than those on the placebo studies, on North Star, stairs climb etc. But they have not been able to get the FDA to take this into account.
  •    They are working with the FDA so that US patients can benefit from this compound too, they are sad people in Latin America can have Translarna but not in the US.

Q:  Following on from the recent data released about increased lung function and the potential benefit for non-ambulatory patients, are you currently using non-ambulatory patients in the extension study, if not, do you plan to?  Also, how long do you anticipate before Ataluren would be given market approval for non-ambulatory patients?

  •    Pulmonary function, by nature is non-ambulatory
  •    PTC is longest in field of Duchenne clinical trials. Some of the patients have been on this drug for 10 years. In this time some patients have lost ambulation. They have monitored pulmonary function and gathered a range of data. They haven’t used placebo controlled, but used natural history data, there is an interesting result, Translarna vs natural history presents a 4 year difference. Ie decline by age 16 with Translarna is similar to the decline by age 12 without the drug, with a 13% improvement in pulmonary function. They are changing the course of the condition downstream and following the progress of the boys.

Q:  Considering the recent partnerships, would you consider a combination approach with other potential compounds and can you tell us your plans for second generation molecules?

  •    The compound is already being used in combination with steroids. There is an improvement that is above and in addition to the effect of the steroids.
  •    They would happily use in combination with a dystrophin replacement.
  •       They have programmes ongoing to develop the next generation of drugs to increase the level of RNA.


Questions from the floor

Q:  During clinical trials, especially the longer ones, if there is no efficacy, is it ethical to continue?

[PTC] data monitoring committee is always looking at safety and utility analysis to consider whether it is worthwhile.

[Italfarmaco] included in study 48, based on MRI after one year of treatment, but that data cannot be shared with the community.

Even in a shorter study this is included in our considerations, especially in open-label studies.

[Pfizer] have a feasibility study

[Phase Bio] only 4 weeks, not a requirement but we are aware of the risk of withholding a potentially therapeutic drug, especially after 4 years

Q:  Will you include Becker in your programmes? Has this been approved by Regulators?

[Sarepta] It has been suggested, for the sake of measurement and assessment, it is preferable to have a homogenous population, therefore they are constrained to exclude Becker.

[Catabasis] There is more natural history now as more patients are coming forward.  Once endpoints that can show efficacy are understood, there can be studies in these populations.

[PTC] It is better to pick a population first, but these are variations across a spectrum so they should benefit from the same treatment.  Becker is a milder form, so it is harder to see a benefit from the therapy, but they hope that patients with Becker will get the treatment once it has been approved.

It is a good idea to define both conditions as dystrophinopathy so that all patients can access the treatment after it has been developed.

Q:  [To Sarepta] Exon 44 skipping, where is the research up to, are there any UK trials?

For exon 44 they have a panel of drugs they are focussing on but they are not in the top three. They envisage an international study but need to get more of a pathway from the Regulator first.

Q:  What are your current biggest hurdles, what is your focus for the next year?

[Akashi] need a pathway from the Regulators to move HT100 forward. They will find out by December 14th what is required.

Q:  What does the DMD community need to do, to get more drugs?

[Sarepta] It would be helpful to understand the natural history better, to understand the deterioration. They need the Regulator to understand the natural history, which could speed up trials.  They are not there yet as need solid data and really hard endpoints.

[Akashi] have two huge challenges, firstly endpoints that are clinically relevant and applicable to all patients. There is not one endpoint that fits all disease stages and will measure the effect of any and every drug. We need to develop ways of measuring the effect of drugs at each stage of the disease, with endpoints that are relevant for that child at that stage (individualized endpoints, categorical outcomes such as “improved” and “not improved”).  The second challenge is the number of patients available for recruitment.  The same clinical centres are recruiting for many studies, and these centres are overwhelmed.  The clinical trial conduct requires close and careful monitoring of patients and sites running too many trials can lose control.  There is a need to create clinical trial readiness at many more centres spread across a wide geographical area in the US (and other countries).

[PHASEBio] are focusing on the heart, and need to define new endpoints.

[Pfizer] are completing recruitment, and are concerned about patient monitoring and whether sites are over-committing.

[Catabasis]  is planning for phase 3 and a study in non-ambulatory patients, and is looking at endpoints.  Multiple companies and academic groups are working together in consortia such as cTAP and C-Path to better understand endpoints and the natural history of the disease.  This will help design better studies. The natural history data is very important for patients to participate in, and will help move research ahead faster.

[PTC] plan to improve access to Translarna globally and also expand this to under-5s and non-ambulatory patients.

[Italfarmaco] want to get their compound up and running, get recruitment started at the end of this year, and get the study going at the start of next year.  They are keen to develop hard endpoints, especially MRI.

Q:  What can patient organisations and families do to support your efforts?

[Italfarmaco] Get involved in patient groups and participate in trials.  They are working closely with advocates, giving reimbursement to families in Italy.

Word of mouth is important, share information among your contacts and communities about clinical trials.  It is a huge burden to come to trial sites and have boys undergo all of these tests, and it is very much appreciated.

[Pfizer] participate in trials, add to the knowledge base of the community.

[PHASEBio] there is a great opportunity to collaborate, define the study and endpoints, give direct feedback from the boys.

[Sarepta] Make sure families understand Duchenne, and politicians and clinicians must listen to patients and learn from them.  We want to know and document and continue to learn from patients.

[Akashi] Participate in Registries. Patients are often taking steroids and many other compounds, and full Registry data allows them to collect data about combinations and the safety of these combinations.  This will help in developing combination therapies. Every person living with Duchenne should be on a Registry.


The Action Duchenne International Conference 2017 will take place across 10, 11 and 12 November in Birmingham at the Hilton NEC.  To contact us, or to register your interest in next year’s conference, please email

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