AACR preview – Novel targets in the spotlight

AACR preview – Novel targets in the spotlight

Source EP Vantage
Company RocheAdvaxisAmgenARMO BioSciencesAstraZenecaAtara BiotherapeuticsBeiGeneBristol-Myers SquibbDaiichi SankyoFive Prime TherapeuticsIgnytaJohnson & JohnsonJuno TherapeuticsKite PharmaLoxo OncologyMerck & CoMerck KGaANational Cancer Institute (NCI; USA)NovartisPfizer 
Tags Comment, Free Content, Trial Results, Cell Therapy, Monoclonal Antibody, Oncology
Date March 18, 2016

The annual meeting of the American Association for Cancer Research has steadily been gaining in importance, and when its latest instalment kicks off in New Orleans next month investors will be watching particularly for initial data from novel cancer immunotherapy mechanisms.

These include first-in-human results for Roche  and  Amgen ’s respective Ox40 agonist  and anti-CSF1R MAb (see table below). More established anti-PD-1/PD-L1 MAbs will feature too, and in  cell therapy  a major symposium on April 19 will focus on CAR-T, while  Kite  will provide more data on its most advanced engineered T-cell receptor project.

The most advanced checkpoint inhibitor results concern overall survival data from Bristol-Myers Squibb ’s Opdivo /Yervoy  combo in melanoma, though this is an approved use. For novel indications look to survival results from Bristol’s Checkmate-141 – a head and neck cancer trial that was  stopped early for efficacy in January.

Approval in head and neck cancer would further extend Opdivo ’s lead over Merck & Co ’s Keytruda , which features at AACR in a presentation of Keynote-006, a trial in first-line melanoma irrespective of Braf status – an approved indication as of December.

And, as new indications go, Keytruda  data in Merkel cell carcinoma will also be presented; this rare cancer type might be the first indication for  Merck KGaA /Pfizer ’s avelumab , which will itself be the subject of results from the Javelin study in solid tumours.

Selected AACR abstracts 
Project  Company  Notes  Trial ID  Abstract 
Keytruda  vs  Yervoy   Merck & Co   Keynote-006, 1st-line melanoma  NCT01866319  CT004 
Keytruda   Merck & Co   Merkel cell carcinoma  NCT02267603  CT096 
Opdivo   Bristol-Myers Squibb   Checkmate-141, squamous head & neck cancer  NCT02105636  CT099 
Avelumab   Merck KGaA /Pfizer   Javelin Solid Tumor study  NCT01772004  CT132 
Axalimogene filolisbac   Advaxis   Listeria -based therapy before robotic surgery   NCT02002182  LB-095 
Beigene -283  Merck KGaA   Raf /Ras mutated tumours  NCT02610361   CT005 
Entrectinib   Ignyta   TKI-naive pts harbouring gene rearrangement  NCT02097810   CT007 
Loxo 101   Loxo Oncology   Solid tumours with NTRK gene fusions   NCT02576431   CT008 
RG7888  (MOXR0916 )   Roche   1st in human Ox40 agonist   NCT02219724  CT097 
AM0010   Armo Biosciences   Pegylated IL-10  NCT02009449   CT098 
AMG 820   Amgen   1st in human anti-CSF1R MAb  NCT01444404   CT137 
JNJ-61610588   Johnson & Johnson   Anti-Vista MAb  NCT02671955   ? 
AZD0156   AstraZeneca   1st in class ATM  kinase inhibitor  NCT02588105  ? 
MBG453   Novartis   Anti-Tim3 MAb  NCT02608268  ? 
Various CAR-Ts  Juno, Novartis  etc  CAR T Cells: New Models in the Showroom  Several  Major symposium 
KTE-C19   Kite   Zuma-1  NCT02348216  CT135 
CD22 CAR-T  NCI  Relevant to Juno  NCT02315612  ? 
Mage A3 TCR   Kite   Metastatic cancer, HLA -A1-positive pts  NCT02153905  CT003 
huEGFRVIII   Novartis   Glioblastoma  NCT02209376     LB-083 
EBV-CTL   Atara  EBV -associated nasopharyngeal carcinoma  NCT00002663  CT136 

For new targets, however, Roche ’s RG7888  and  Amgen ’s AMG 820  could get the most attention. Not only has there been precious little data so far from agents acting on immune  checkpoints  beyond  PD-1 /PD-L1 and CTLA4 , but investors will also note potential readacross to other assets.

For instance, AstraZeneca  has a competing  anti-Ox40  MAb,  MEDI6469 , while the anti-CSF1R mechanism of AMG 820  is relevant to Five Prime’s  FPA008 , which acts the same way. AMG 820  is separately in a combo trial with  Keytruda , which is also being combined with Daiichi Sankyo 's PLX3397 , a CSF1R  tyrosine kinase inhibitor .

Other novel mechanisms – including Johnson & Johnson ’s anti-Vista MAb, Astra 's Ataxia telangiectasia mutated (ATM ) kinase inhibitor and Novartis ’s anti-Tim3 MAb – will also feature at AACR, though it is not clear at present whether any clinical data will be presented.

Second chance

The 2015 AACR meeting was the venue for the first major disappointment for CAR-T therapies in solid tumours – specifically in mesothelioma with Novartis ’s CART -meso (AACR – Solid tumour CAR-T foray lives up to its low-key billing, April 20, 2015).

This year provides a second chance. In addition to a special CAR-T symposium, three cell therapy  sessions will be of interest to investors in  Kite Pharma  and Juno. The former will present an update on the potentially pivotal Zuma-1 trial of  KTE-C19  and clinical data on its first engineered T-cell receptor project, targeting the  Mage  A3 antigen and  licensed for $1.2m from the NCI last October.

Juno will have preclinical presentations, but an update from the NCI’s anti-CD22 CAR-T project will be relevant, since Juno now holds rights to this construct, having licensed it from Opus Bio as JCAR018 . Particularly important will be the extent of any benefit in patients relapsing on initial CD19 -directed CAR-T therapy.

For now, however, with just abstract headlines and some abstract texts unveiled, share price reactions have been muted – with one exception: Advaxis  has traded up 29% over the past month on the revelation that its  listeria -based therapy axalimogene filolisbac  would feature in a late-breaker. The company was hit by a US clinical hold last year, though this was lifted in December.

Given how important early-stage data are becoming for oncology projects there should be plenty more scope for share price movement once the AACR gets under way.

EP Vantage will be reporting from New Orleans, where the AACR conference begins on April 16.

Interview – Galvani wants to get on patients’ nerves

Interview – Galvani wants to get on patients’ nerves

Source EP Vantage
Company GlaxoSmithKlineBoston ScientificCVRxImThera MedicalLivaNovaMedtronicSetPoint MedicalSt. Jude Medical 
Tags Analysis, Company Strategy, Medtech, Musculoskeletal, Gastro-Intestinal, Endocrine, Joint Venture, Free Content, Interview
Date August 04, 2016

GlaxoSmithKline  had already signalled its interest in  bioelectronics  by starting an investment group three years ago that focused on this area. Now it is beginning to develop these devices directly, through Galvani  Bioelectronics , a joint venture it has established with Google’s life sciences arm Verily.

The partners intend to invest £540m ($709m) in Galvani over the next seven years, dependent on milestones, and  test bioelectronics  in areas like diabetes. “Formation of Galvani  Bioelectronics  is a huge undertaking by both GSK and Verily,” says Kris Famm, president of the new group.

“There’s definitely a degree of outstanding risk. But it behoves companies in general to look at the long-term horizon and see what can have meaningful impact not only on one or two products but what could open up a whole new class.”

Glaxo  will hold 55% of the equity interest in the UK-based group and Verily 45%.

Bioelectronics  is similar to neuromodulation, involving the use of implanted devices to stimulate or block neural impulses. Neuromodulation is well established for neurological conditions such as chronic pain and the tremor associated with Parkinson’s disease.  Bioelectronics  seeks to adapt the technique to a much wider range of disorders.

Galvani is going where the money is, with development programmes in metabolic, inflammatory and endocrine disorders, with type 2 diabetes being one example. Galvani contends that there are several ways in which altering neural function can treat this condition.

“You can shift pancreatic function through modulation of the nervous signals to the pancreas,” says Mr Famm. “You can shift the sensitivity to insulin in different tissues through modulating the sensing of insulin in the body; you can shift, potentially, storage of glucose through innervation to organs such as the liver; you can shift the uptake of nutrition and satiety through innervation of the stomach and the gastrointestinal tract.

“There are many different potential points of attack. We’ve been exploring several of those and have good reason to believe, in animal models, that we can get some powerful effects.”

Read and write

Animal models is as far as the company has got. It has bold ambitions: data from the first clinical proof of concept trials in three years and a finished device ready for regulatory review seven years from now.

Still, 2023 is a while away, and another company has already reached the clinical stage with a similar technology. Last month SetPoint Medical  reported encouraging, if not definitive, results with its vagus nerve stimulation device in patients with rheumatoid arthritis (Interview – SetPoint off to a good start in the clinic, July 21, 2016).

Far from being left behind, however, GlaxoSmithKline  in fact stands to benefit from SetPoint’s success. It is one of SetPoint’s venture backers, having sunk $5m into the start-up three years ago through its dedicated  bioelectronics  investment fund, Action Potential Venture Capital.

Galvani intends to employ a similar initial clinical strategy to SetPoint, using a third-party device at first – SetPoint has adapted a vagus nerve stimulator from Cyberonics, while Galvani is using a device from Nuviant Medical. It will simultaneously work on a proprietary version.

There are differences, however. SetPoint’s implant is miniaturised compared with traditional neuromodulation devices, Mr Famm says. But Galvani is even further along on that trajectory, building smaller and smaller devices, thanks to Verily’s engineering expertise.

The company wants “devices that can stimulate not just a particular waveform, but devices that can record the underlying neuro signals as well,” he says. A video dating from 2014 suggests that  Glaxo  wants to “read and write action potentials”. The collaboration has mentioned incorporating Verily’s data analytics capacity – perhaps Galvani needs this in  order  to better understand neural impulses as well as altering them.


Another difference between Galvani and SetPoint is the positioning of the modulators. “SetPoint have this stimulating on the cervical vagus,” Mr Famm says. “Our view is that the closer we can be to the end organ the more specific an effect we can have, without affecting the many other functions that run through the trunk or the vagus nerve in the neck.”

But this presents problems of its own, not least how to power the device. “It will be wirelessly charged,” says Mr Famm. “It is critical to do deep tissue charging without too much power loss.” Again, Verily will be contributing technology and knowhow here.

As for the competitive landscape, there are several device companies working on peripheral neurostimulation. CVRx  is developing a device to simulate the carotid sinus to treat hypertension and heart failure and  ImThera Medical  is working on stimulating the hypoglossal nerve in the neck as a therapy for obstructive sleep apnoea.

And then there are the big players: Medtronic  and Boston Scientific, St Jude, Cyberonics and  LivaNova  all have neuromodulation franchises, though as Mr Famm points out, “they haven’t pursued – at least publicly – the realm of neuromodulation in the viscera for the sort of indications that are traditionally treated with medicines.”

Glaxo  is the first pharma company to show an interest in this approach. Mr Famm believes it will not be the last.

He says that it is inevitable that other large pharmaceutical companies will see the potential of bioelectronics  and begin to investigate this technique. Presumably the looming threat of biosimilar competition to blockbusters like  Sanofi ’s diabetes drug Lantus  and J&J’s arthritis antibody  Remicade  will spur the search for alternative products.

“Who moves in remains to be seen, and in what sort of partnerships, but if the field has the potential we believe it has, and we continue to be successful in the next few years, of course there will be other players,” says Mr Famm.

The success or otherwise of bioelectronics  in general and Galvani in particular will naturally hinge on clinical data. Come 2019,  Glaxo  will have a decent idea of whether its faith has been justified.


Upcoming events – Schizophrenia and tinnitus data from Intra-celluar and Auris

Upcoming events – Schizophrenia and tinnitus data from Intra-celluar and Auris

Source EP Vantage
Company Intra-Cellular TherapiesAuris Medical 
Tags Analysis, Company Strategy, Phase III, Sensory Organs, Central Nervous System, Free Content, Event - Open
Date August 05, 2016

Welcome to your weekly digest of approaching regulatory and clinical readouts. In the fourth quarter results are due from the second phase III schizophrenia trial of Intra-cellular’s ITI-007 , which in its first study proved effective and, most importantly, free from the side effects associated with older antipsychotics. A repeat would reaffirm its blockbuster potential.

Meanwhile, topline results from the phase III TACTT2 trial of Auris  Medical’s tinnitus candidate  AM-101  are expected in August. A European trial is also due to report before the end of the year. These could put it on track to become the first drug approved for the acute form of the disease, though earlier clinical data were mixed.

Pipeline in a drug

Intra-cellular's second phase III study is in 696 schizophrenia patients experiencing an acute exacerbation of psychosis, and subjects will receive 60mg or 20mg ITI-007 , the active control risperidone  (4mg), or placebo. The oral treatment will be given once a day in the morning for six  weeks .

The primary endpoint is change from baseline at day 42 on the positive and negative symptom scale (PANSS) total score, and the key secondary endpoint is change in clinical global impression scale for severity of illness (CGI-S). When the first phase III trial reported positive results last September the company’s shares rocketed 87%.

In that trial 40mg and 60mg were given over four weeks  versus placebo; the higher dose showed a statistically significantly greater improvement in the PANSS score. The improvement was seen after one week of treatment  (Intra-Cellular’s schizophrenia success could tempt a buyer, September 17, 2015).

The project had no major side-effects and seemed free from the metabolic issues seen with some older drugs – it did not lead to weight gain or changes in metabolic measures.

ITI-007  is Intra-cellular’s lead asset, and is also in trials for bipolar disorder and agitation in dementia, with preclinical work in other mood disorders. According to  EvaluatePharma’s consensus 2022 worldwide sales are forecast to reach $2.5bn, $1bn of which are through partnering the drug in Europe. It has an NPV of $3.4bn, nearly double Intra-cellular’s market cap.

It is wholly owned by the company, but partnering is essential to generating peak sales, and positive results could attract a buyer. ITI-007  is likely to be a first-line treatment, but availability of generic antipsychotics could affect its use in clinical practice.

ITI-007  will need to play on its impressive side-effect profile to claw out a place in the market. The top branded players are injectables, often with monthly dosing; preclinical work on a long-acting injectable version of  ITI-007  has started.

All ears for tinnitus data

The co-primary endpoints in Auris 's phase III TACTT2 trial are change in tinnitus loudness and the tinnitus functional index score, which measures tinnitus impact and burden, from baseline to day 84.

AM-101 , also known as Keyzilen, is an NMDA receptor antagonist  designed to suppress aberrant excitation of the auditory nerve that is thought to underlie the development of tinnitus.

There are no treatments approved for the disorder, but commonly used agents include oral corticosteroids, ginkgo biloba  and benzodiazepines, as is masking by another stimulus. 84% of US ear, nose and throat physicians are dissatisfied with these, according to LifeSci Capital analysts.

If AM-101  succeeds it will hit a market ripe for disruption. But the signals so far have been mixed: a phase II trial failed to show a treatment benefit on its primary endpoint of minimal masking level – the lowest level at which the tinnitus can be masked by a stimulus – although it did hit other endpoints including tinnitus loudness  (Upcoming events: MEI’s HDAC inhibitor data and futility from Auris in tinnitus, March 6, 2015). 

AM-101  is also in a European trial, TACTT3, expected to report results in the fourth quarter. This has a similar design to TACTT2, but includes a second  cohort  evaluating patients with post-acute tinnitus between three and 12 months from onset.

Auris  will likely wait until the TACTT3 data are available before  filing  the project with the FDA, Leerink analysts believe. They give it a 60% chance of success and put peak risk-adjusted sales at $350m.

LifeSci Capital analysts are more optimistic, saying the potential US market size for AM-101  is up to $630m. The acute form of the disease affects around 500,000 people in the US. The analysts note that the volume of patients could increase if an effective treatment becomes available.

Auris  is also developing  AM-111 , which is in phase III for treating acute sensorineural hearing loss.

Project  Study  Trial ID 
ITI-007   ITI-007 -301
ITI-007 -302 (second trial) 
AM-101   TACTT2 (North America)
TACTT3 (Europe) 
AM-101   AMPACT1 (Open label extension to TACTT2)


Bristol swings for the fences and strikes out

Bristol swings for the fences and strikes out

Source EP Vantage
Company Bristol-Myers SquibbAstraZenecaMerck & CoOno PharmaceuticalRoche 
Tags Comment, Company Strategy, Trial Results, Phase III, Launches, Monoclonal Antibody, Immunology, Oncology, Free Content, Clinical Setback
Date August 05, 2016

Since the first anti-PD-1 agents secured approvals the first-line lung cancer indication has represented the biggest prize on offer. Today Bristol-Myers Squibb  paid the price for overreaching with  Opdivo  and trying to knock  Merck & Co ’s Keytruda , which had a slight time advantage, out of the park.

The failure of Bristol’s Checkmate-026 trial is a huge blow for the group, whose stock crashed 17% this morning – losing $20bn of market cap – while Merck  climbed 7%. Bristol now awaits results of a  Yervoy  combo study in this setting, after what looks like immuno-oncology’s biggest upset so far.

It is very easy to say in hindsight, but the problem with Checkmate-026, an open-label trial testing Opdivo in 535 first-line NSCLC patients, was its design. Bristol had moved aggressively, recruiting relatively low PD-L1 -expressing patients, and the first analysis concerned 5% or higher expressers, with the primary endpoint set at progression-free in preference to overall survival.

Perhaps it was just bad luck, or maybe Bristol had feared falling behind Keytruda . The Merck  drug’s first-line NSCLC trial,  Keynote-024, rendered a positive topline result in June, hitting both co-primary endpoints of PFS and OS – but in patients expressing PD-L1  at 50% or above.

Until today the battle was playing out exactly as the sellside had expected. Keytruda  was to be first to yield positive first-line NSCLC data in a narrow patient population, before  Opdivo  regained the upper hand with a benefit in lower  PD-L1  expressers.

Indeed, on its second-quarter conference call just a week ago, Bristol was still boasting how Checkmate-026 could allow it to broaden the patient population further: if >5% expressers yielded positive data the company could look at the effect in those with PD-L1  at >1%, representing 70% of first-line patients.

Moreover, a positive PFS benefit could be backed up by OS data, a secondary endpoint. “And we can still file without a positive OS result,” said Bristol’s chief scientific officer, Francis Cuss.

Now, with Bristol today saying Checkmate-026 was a bust, failing to show a PFS benefit in the 5% or greater PD-L1 -expressing population, the rulebook has been torn up.

Early worries

Still, there had been worries among some analysts about an initial reliance on PFS. On Bristol’s fourth-quarter call Citi’s Andrew Baum specifically raised the issue of so-called “pseudoprogression” – a known problem with some previous immuno-oncology trials that had obscured a potential benefit by making it seem like active patients were progressing as fast as the control group.

But realistically Bristol probably had little choice but to go with PFS. Waiting for an OS benefit to mature would have been unrealistic in a first-line study with the breadth of Checkpoint-026.

As it is Bristol might now try to cut the patient population down, looking at only the 50% or higher expressers, but since this had not been specified in the design of Checkmate-026 it would be exploratory, and would hold little water as regards regulatory filings.

Most likely Opdivo  will for now be restricted to second-line use, an approved indication, with first-line reserved for  Keytruda  in its biomarker subgroup.  Checkmate-227, a complex first-line NSCLC trial involving several combinations as well as Opdivo  monotherapy, is under way but does not read out until 2018.

Anti-PD-1/PD-L1 MAb approvals in major Western markets 
Approval  date  Region  Therapy  Indication  Notes 
Tecentriq  (Roche) 
18 May 2016  US  Monotherapy  2nd-line urothelial  carcinoma  IMvigor 210 study 
Opdivo  (Bristol-Myers  Squibb /Ono ) 
17 May 2016  US  Monotherapy  3rd-line classical Hodgkin lymphoma   CheckMate-205 & 039 studies 
11 May 2016  EU  Yervoy  combo  1st-line melanoma regardless of Braf status  Checkmate-067 & 069 studies 
6 Apr 2016  EU  Monotherapy  2nd-line renal cell carcinoma  Checkmate-025 study 
6 Apr 2016  EU  Monotherapy  2nd-line non-squamous NSCLC  Checkmate-057 study 
23 Jan 2016  US  Yervoy  combo  1st-line Braf-positive melanoma   Checkmate-067 study 
23 Jan 2016  US  Monotherapy  1st-line Braf-positive melanoma   Complete response letter on 27 Nov 2015 
24 Nov 2015  US  Monotherapy  2nd-line renal cell carcinoma  First anti-PD1 to show OS benefit in renal cancer 
24 Nov 2015  US  Monotherapy  1st-line Braf-W/T melanoma  Checkmate-066 study 
9 Oct 2015  US  Monotherapy  2nd-line non-squamous NSCLC  Checkmate-057 study 
1 Oct 2015  US  Yervoy  combo  1st-line Braf-W/T melanoma  1st I-O combo in cancer; Checkmate-069 
20 Jul 2015  EU  Monotherapy  2nd-line squamous NSCLC  – 
19 Jun 2015  EU  Monotherapy  1st & 2nd-line melanoma regardless of Braf status  Checkmate-066 & 037 studies 
4 Mar 2015  US  Monotherapy  2nd-line squamous NSCLC  Checkmate-017 study 
22 Dec 2014  US  Monotherapy  2nd-line melanoma  First US approval ; Checkmate-037 study 
Keytruda  (Merck  & Co) 
2 Aug 2016  EU  Monotherapy  2nd-line PD-L1 -positive NSCLC  Keynote-010 
18 Dec 2015  US  Monotherapy  1st-line melanoma regardless of Braf status  Keynote-006 study 
2 Oct 2015  US  Monotherapy  2nd-line PD-L1 -positive NSCLC  Keynote-001 study 
22 Jul 2015  EU  Monotherapy  1st & 2nd-line melanoma regardless of Braf status  Keynote-001, 002 & 006 studies 
4 Sep 2014  US  Monotherapy  2nd-line melanoma  First anti-PD-1 agent to get US approval ; Keynote-001 study 

As well as Merck  making strong gains,  AstraZeneca  and  Roche  shares spiked today, up 6% and 2% initially, though the UK group quickly faded (Therapy focus – First-line lung cancer is an Opdivo vs Keytruda showdown, June 10, 2016).

Until now EvaluatePharma’s consensus of sellside forecasts saw Bristol generating 60% of 2022  Opdivo  sales in NSCLC, across all lines of therapy. Evercore ISI’s Mark Schoenebaum put the size of the first-line NSCLC market at over $12bn, and neatly summed up the Checkmate-026 failure, calling it “possibly the biggest clinical surprise of my career”.

The consensus-based NPV of Opdivo  in all forecast uses amounted to a staggering $71bn, or 57% of Bristol’s market cap; little wonder that the selloff was so extreme today.

In terms of market cap gains and losses there have been other immuno-oncology rollercoaster moments, including Opdivo  snatching  Keytruda ’s early lead away from it, and Bristol reporting underwhelming and somewhat confusing biomarker data in a second-line NSCLC trial at last year’s Asco meeting; in hindsight perhaps this was the canary in the coalmine.

While much more work still needs to be done to elucidate the importance of various biomarkers, the Checkmate-026 disappointment has triggered a massive shift in sentiment.


Interview – Istar flies towards next-gen glaucoma surgery device

Interview – Istar flies towards next-gen glaucoma surgery device

Source EP Vantage
Company iSTAR MedicalAllerganAqueSysGlaukosInnFocusIvantisNovartisSanten PharmaceuticalTranscend Medical 
Tags Analysis, Company Strategy, Europe, USA, Medtech, Sensory Organs, Free Content, Interview
Date August 08, 2016

Some might feel that the Belgian minimally invasive glaucoma surgery (MIGS) device developer Istar Medical  has missed the boat, with three of its rivals already acquired (see table below). But its chief executive, Michel Vanbrabant, is unperturbed.

“We are behind, it’s true,” he tells EP Vantage. “But I think we bring to the equation a next-generation MIGS solution, which will raise the bar significantly over current-generation MIGS in terms of response rate.”

This improved performance, he says, is enabled by the material used in Istar’s device, which was originally developed by the University of Washington in Seattle before being licensed to the company. “It exhibits very different properties to traditional implants when inserted into the human body.”

Better drainage?

Increased pressure in the eye can damage the optic nerve and lead to glaucoma. MIGS products aim to reduce this by allowing excess intraocular liquid, called aqueous humour, to drain away.

However, current devices – including the two that are FDA-approved, Glaukos ’s iStent and Novartis /Alcon ’s CyPass Micro-Stent – lead to fibrosis in 20-25% of patients because “all of them use hard material that triggers some fibrotic responses in the eye”, Mr Vanbrabant says.

Istar's material is softer and more flexible, so is not associated with this issue, according to the company. The faster speed of drainage through a single stent or tube could also contribute to scarring with the first-generation devices, the chief executive adds.

While Istar's technology acts like a shunt, “it is not a tube or stent but provides thousands of small conduits for aqueous humour to flow through”, Mr Vanbrabant says, which is more like the fluid drainage seen in healthy tissue.

The implant also integrates with the patient’s own tissue “to support drainage without blockage”, he adds. All of these properties “reduce the incidence of fibrosis, minimise scarring, and increase implant performance over time".

This company believes that this should allow the product to capture market share from existing devices once it reaches the market.

It still has some way to go. So far, the company has been focused on its CE-marked STARflo device, but this will shift in the near future to its newer product, MINIject. STARflo has been used to prove the concept, but is not suitable for wide commercialisation because it needs to be implanted by specialised surgeons using traditional surgical techniques.

MINIject shift

MINIject is the commercial product. It comes on a premounted delivery system, making it easier to implant as well as less invasive, and can be delivered by cataract surgeons as well as glaucoma surgeons, increasing the user base, Mr Vanbrabant says.

STARflo is in a multicentre European trial due to report results in the first half of 2017 – if successful, it will pave the way for the more user-friendly MINIject, which is set to start its first human trial by the end of this year. European trial data on MINIject should be available in 2018, at which point iSTAR plans to apply to the FDA for permission to start a US study.

The group raised a €10m ($11m) series B  in April and has enough cash to take it to CE marking MINIject, at which point it will need more funds to commercialise the product in Europe, as well as to carry out the US trial.

Istar might opt to sell the device itself in the EU, though a US partnership could be on the cards. But a trade sale seems to be what the company is working towards.

Companies with approved MIGS devices 
Originator  Acquirer  Device  EU status  US status 
Glaukos   iStent  CE marked 2004  PMA granted June 2012 
Transcend Medical   Novartis /Alcon   CyPass Micro-Stent  CE marked 2009  PMA approval  granted July 2016 
Aquesys   Allergan   Xen45  CE marked  Filed; 510(k) clearance expected late 2016 
Ivantis   Hydrus Microstent  CE marked June 2011  Not yet filed 
Innfocus   Santen   MicroShunt  CE marked January 2012  Not yet filed 
Istar  STARflo/MINIject  CE marked July 2012  Not yet filed 

Istar is already in touch with potential partners; Mr Vanbrabant says: “I don’t think there’s more than one major player that we’re not in contact with.” This includes the companies that have already made acquisitions, which “need to improve the technology that they either just acquired or plan to acquire.”

As for smaller companies, there are several of these behind Istar in terms of development. These have produced “concepts that are very different from our biomaterial – but nothing I was convinced of”, the chief exec says.

“So there is high competition, but the competition is first and foremost coming from GlaukosAlcon  and  Allergan  – who will more likely be creating the market for MIGS as opposed to being a competitor to us when we hit the road two or three years from now.”

The MIGS sector is likely to stay hot with an ageing population and issues with glaucoma drugs, including low compliance. If it does, and Istar proves that its product has an edge over existing devices, it could soon see interest from the big players.

This story has been changed to reflect the fact that the CyPass Micro-Stent received  PMA  approval .