24 MAR 2016
Manchester-based Epiphany, which was founded by managing partner Tim Dempsey in 2011, reached a £30m milestone with its latest transactions and has further deals worth £3.5m nearing completion.
The head of corporate finance house Epiphany Capital has hailed the strength of the north west’s technology and life sciences sectors as it enjoys its busiest-ever start to a year.
Manchester-based Epiphany, which was founded by managing partner Tim Dempsey in 2011, reached a £30m milestone with its latest transactions and has further deals worth £3.5m nearing completion.
Tim advised on January’s £5.5m investment boost from Oxford Capital, Draper Esprit and Partech Ventures for Manchester-based PushDoctor, which has developed an online, on-demand GP surgery.
He also put together a £775,000 growth capital deal for Leeds-based Instrumentel, which develops electronics systems for precision measurement in the rail industry.
The deal was supported by Alycidon Capital and Manchester Venture Partners, which is Epiphany’s sidecar fund.
Beyond the north west, Tim has advised companies including SuperCarers.com, a marketplace which connects families with expert home carers, and Faceshift, a Zurich-based motion capture company behind technology which features in the latest Star Wars film.
Tim said Epiphany’s pipeline remains strong, adding: “We’re seeing a greater level and higher quality of deal flow across northern England. The north west in particular has really upped its game in technology and life sciences.
“It’s a really exciting region in which to operate and I’m confident that we can bring more top-tier venture capital to the region which will, in turn help the region to produce more global leaders.”
Epiphany has now advised on 23 fundraising deals in the technology and life sciences sectors, with a focus on fast-growing, early-stage companies that have the ability to make a significant impact in their markets.
Tim said: “Our strategy is to become closely aligned with these companies and utilise our strong relationships with the venture capital community to put deals together, allowing management teams to concentrate on growing their businesses while we take care of their funding requirements.
“Our main focus is on ‘enabling’ technologies in financial services, consumer health, connected medical devices, e-commerce, artificial intelligence and the internet of things – all areas which reflect our changing lifestyles.”
Epiphany is supported by a team of experienced advisers that includes Dr Ian Evetts, a former evaluations director at AstraZeneca.
The round was jointly led by Oxford Capital Partners and Draper Esprit, alongside Partech Ventures. The Company now sits with global disrupters including Lyst and TrustPilot, in the stables that have previously been the home of Skype, Baidu and Tesla.
PushDoctor.co.uk is changing the way everyone can access healthcare using its on-demand online GP surgery, making healthcare accessible for the tens of millions of people in the UK who find seeing a doctor difficult.
The Care Quality Commission-regulated and NHS-commissioned service allows patients to book and attend secure video GP appointments seven days per week, 365 days of the year, via a website and iOS app.
The Company had previously raised a $1.2 million seed round, also advised by Epiphany, now bringing its total funding to date to $9.4million.
PushDoctor.co.uk plans to use the investment to strengthen its brand position as category leader, carry out further product innovations, expand the business’ management structure, including making key marketing and product hires and to further its industry-connectivity; offering patients a simpler and more powerful set of routes into the healthcare eco-system.
The business was established in early 2013, after its founder fell ill while in the US, struggled to get a doctor’s appointment and noticed a gap in the market for primary care from UK-based doctors on the go. PushDoctor became the first On-Demand Remote Care provider to launch in the UK App Store. PushDoctor.co.uk has since grown to become the fastest-growing clinician network in the country.
The platform enables patients to connect to qualified GMC registered private GPs in minutes in a HIPAA-approved video-surgery, and patients benefit from instant access to professional medical advice from a UK doctor who can prescribe, refer or provide a sick note.
The service charges £25 for a 10-minute appointment with a General Medical Council-regulated GP, while prescriptions are £4.50 and referral letters or fit for work notes are £12.50.
PushDoctor.co.uk was advised by Tim Dempsey of Epiphany Capital and Jonathan Gillow from Hill Dickinson LLP whilst Oxford Capital Partners and Draper Esprit were advised by Barry Maytum of Keystone Law LLP.
For more information on this deal, please contact Tim Dempsey
Several countries around the world, including the UK, now face the prospect of an ageing population that is expanding, which is putting increasing demand on healthcare services.
The rise in the number of cases of diabetes and obesity worldwide is also creating demand for medical services, particularly in emerging markets.
FE Analytics shows that in the past year to June 29 the MSCI World Health Care index gained 26.42 per cent, rising more than most major regional indices. Over the same period, the Nikkei 225 gained 19 per cent, while the S&P 500 was up 15.04 per cent.
This might go some way to explain why the AIC Sector Specialist: Biotechnology & Healthcare sector has been the best performing investment trust sector over one, three, five and 10 years, the Association of Investment Companies (AIC) says.
At a recent AIC roundtable on the biotechnology and healthcare sector, Daniel Mahony, manager of Polar Capital Global Healthcare Growth and Income, commented: “Governments and insurers need to find ways of delivering more healthcare to more people for less, or the same, money.”
He believes this has resulted in two investment trends that he defines as “consolidators” – those companies taking the costs out of healthcare systems – and “innovators”, which are firms developing products and services that disrupt existing systems and improve the quality of healthcare.
Biotech stocks are known for their volatility, with the sector overheating at times. But Sam Isaly, managing partner at OrbiMed Advisors and manager of the Worldwide Healthcare Trust, asserts that biotechnology companies of all sizes are making significant leaps. He points to several instances where they have come to market with “blockbuster” drugs in areas such as oncology and hepatitis C.
Mr Isaly adds: “A continued increase in spending and consumption of healthcare services on a worldwide basis mean that near-term fundamentals for the healthcare sector are as positive as ever.”
Grant Bowers, portfolio manager of the Franklin US Opportunities Fund, agrees. He observes that US companies have upped their research and development efforts, prompting the discovery of new cures and treatments.
But he acknowledges: “These opportunities are not just in the pharmaceutical and biotech space; we also believe prospects are bright for businesses that provide healthcare services, tools or diagnostics.”
The increased need for healthcare services and support in emerging markets is a trend Hilary Natoff, manager of the Fidelity Funds’ Global Health Care Fund, is keeping an eye on.
She explains: “Multinational healthcare companies typically generate 20 per cent of their revenues from emerging markets and this could increase significantly, with China’s healthcare market growing at an annualised rate of 20 per cent.
“Factoring in this potential growth, valuations do not seem as expensive. Similarly, many healthcare companies have strong balance sheets and high cash reserves, increasing the possibility of more deals in the sector.”
The £775k growth capital deal was led by private office, Alycidon Capital, who were joined by the University of Leeds, and Manchester Venture Partners (Epiphany’s side-car fund).
Instrumentel has a strong presence in the rail industry, the company has undertaken high value projects for major players including Angel Trains, East Coast Trains, First ScotRail and London Underground.
For more information on this deal, please contact Tim Dempsey.
Pharmaphorum 27 June 2016
Paul Tunnah speaks with industry veteran, and guest facilitator, Ian Evetts on what big pharma can learn from the biotech sector about delivering medicines of value to market.
As the pharma industry faces increasing pressure to develop and launch new medicines that are not only efficacious, but can also deliver value for money to ailing global healthcare systems, its relationship with biotech has never been more critical for ensuring post-patent cliff pipelines can be adequately replenished to allow continued innovation to be brought to market.
Here, pharmaphorum speaks with Ian Evetts, an industry veteran with experience on both the biotech and pharma sides of the fence, to hear his thoughts on how pharma can accurately assess the value of early-stage assets, how biotech and big pharma look at things differently and how they can learn from each other to meet these new challenges.
“It is important to make an informed view of the profile of a successful product at the time of launch”
PT: What are the biggest challenges in assessing medicines value at an early stage?
IE: We need to distinguish between asset valuation and long-term forecasting, which is a component within that. The value of an asset depends on numerous factors, including clinical attributes, level of future unmet need, commercial factors related to the asset and the market it is entering, strategic fit within a pipeline, the degree of technical risk and the expected return on investment.
To determine the commercial value for an early stage asset, long-term forecasting is clearly critical, yet it is complex – good forecasting is about increasing the accuracy of prediction; matching the most likely product profile against the predicted unmet needs at the time of launch, given the numerous uncertainties that lie ahead. It’s also about appropriate profiling and benchmarking – considering all relevant market drivers to enhance the relevance of your prediction. The most fundamental pitfall when forecasting for an early stage asset is to forecast value around current unmet needs, rather than those 10-15 years down the line.
Of course, it is almost impossible to second guess which development candidates will pass or fail clinical hurdles, but it is important to make an informed view of the profile of a successful product at the time of launch – and defining what we mean by ‘success’. In addition, it is important to understand the global picture – the impact of emerging markets and trends within established ones; the shifting treatment paradigms and disease prevalence patterns – as all markets are different and often respond to different product profiles.
It is also naïve to dismiss future pricing, reimbursement and market access considerations for an early-stage asset – too many products are progressed without early insight to the likely acceptance of a product within the market – not from a regulatory perspective, but relating to likely pricing and access barriers.
“Biotech valuations are clearly nimbler and have easier connectivity across technical and commercial functions”
PT: Do biotech and big pharma fundamentally assess value differently?
IE: From a general perspective, there is a fundamental difference in the end-points for asset valuation. Big pharma takes a longer term view, whereas biotech companies are normally looking to satisfy investors who are working to short-term ROI (usually based on a five year exit strategy).
Clearly, emerging biotechs are looking to convince potential investors and licensees of the value of their asset and there is a tendency to over-egg the likely sales potential though crude forecasting approaches or use of selective data. Within major pharma, in-house assets can be subject to political drivers as much as sound techno-commercial-based valuation – poor use of considered, independent assessment and too much reliance on therapy area teams who are vying for funds. What tends to be common for both biotech and major pharma is an inflated valuation of most assets and a tendency to continue development for too long, where the real future value is insufficient.
In terms of the processes, big pharma invariably has large cross-functional teams and well-defined process that are, on paper, efficient mechanisms for understanding value and directing medicines development, but in practice are too large & unwieldy, too slow and too politically charged. Biotech valuations are clearly nimbler and, with smaller teams and a focus on delivery, have easier connectivity across technical and commercial functions. Asset development – and, therefore, valuation – focuses on investors and licensees, as previously mentioned, but there is often a low-level of understanding of major pharma needs and processes.
“In the ideal world, individuals and valuation teams need a blend of commercial acumen with scientific understanding”
So biotechs need to ensure that their programmes are satisfactory for investors, pharma licensees, regulators and payers. It’s a misconception that a biotech can ignore market access considerations, for example, because they are looking for an exit by phase II. Ultimately, the drug has to be saleable – having activity against a target is not enough.
PT: At what stage in drug development should commercial take the lead from science?
IE: It’s all about getting an appropriate balance throughout the discovery and development programme. Targets should be selected on the basis of sound strategy and this should be driven by techno-commercial foresight. It is a myth to assume that, ‘if a product works, it will sell’. Good products fail because of poor alignment to commercial factors due to a lack of early, clear direction and consideration.
So, commercial leadership should exist right at the start, followed by strong representation from clinical, technical and commercial functions throughout the whole process, ensuring viable early stage discovery targets, development of clinical programmes that marry with marketable opportunities and into late-stage clinical positioning and pricing – although the balance shifts as a drug is progressed through development stages, the commercial role can never be down-played.
Of course, there are many issues that can interfere with this alignment and it’s easy to point the finger of blame at leadership when things go wrong. In the ideal world, individuals and valuation teams need a blend of commercial acumen with scientific understanding. Without this, a drug can still be commercially successful, but it’s likely to be by chance!
PT: How are market access challenges impacting assessment of medicines’ value?
IE: Significantly. Good science and efficacious drugs are no longer enough and there is effectively no product if an innovation cannot satisfy national pricing bodies’ requirements for premium pricing against their standard of care. Poor understanding of the pricing and reimbursement picture in all relevant markets for a novel drug represents a huge oversight – and one which is often associated with those late-stage opportunities that remain un-partnered. It is imperative that appropriate clinical trials are developed for countries of high value to a brand – and this includes selection of active comparators in phase IIb and phase III trials. Also, trial programmes that satisfy regulators and payers don’t necessarily translate into good market uptake – market access can still remain an issue if data does not resonate with end-users.
“Size dictates both the benefits and flaws of biotech and big pharma!”
The reality is that regulatory approval is just the first step in a long sequence of events which dictate commercial success, from national pricing and reimbursement assessment through to regional and local payer decisions. The health economic package associated with a phase III programme is critical to a drug’s success. Sometimes, even with a good health economic case, deals need to be struck with national payers on pricing; pre-launch buy-in from all prescribers and payers is critical to ensure sufficient value can be retained on market.
PT: What can big pharma learn most from biotech about delivering value?
IE: Size dictates both the benefits and flaws of biotech and big pharma! The biotech ethos is all about fast decision-making, less political involvement in assessments, use of fast-track or streamlined development programmes with key data as priority and less concern over risk-taking – keeping several marketable options open from the outset
For portfolio decision making and asset valuation, maybe big pharma could adopt a strategy to utilise small, highly-skilled, techno-commercial teams with cross-functional expertise who are independent of therapy area and business development groups, but affiliated to them.
15th May 2015
Ian Evetts joins Glythera with over 20 years experience in the Pharmaceutical industry. He has a track record of senior strategic and operational roles including, Managing Director at Atebion BDS Ltd, Strategic Advisor at Bionure and Business Development and Portfolio Director at AstraZeneca. As Commercial Director of Glythera, he will provide strategic advice on developing the company’s technologies and therapies, a key growth area for Glythera.
Commenting on his appointment, Ian Evetts said, “Glythera is an innovative biotechnology company and their proprietary linker and stable glycan technologies represent a leap forward in the development of next generation therapies. I am extremely pleased to be involved at this exciting time for the company and I look forward to working with the team as it continues to expand and maximise new opportunities.”
27th July 2015
Glythera-led consortium wins Industrial Biotechnology Catalyst funding £248,000 to develop high-throughput glycosylation assay Glythera Limited, the next generation Antibody Drug Conjugate (ADC) company, today announces that, through a consortium with GlycoSeLect Ltd, specialists in the development and production of recombinant prokaryotic lectins and the Biologics unit of the Centre for Process Innovation (CPI), a UK-based technology innovation centre and part of the High Value Manufacturing Catapult, they have been awarded £248,000 by Innovate UK, the UK…government’s innovation agency, to develop a high-throughput glycosylation assay to facilitate the development of next generation biological therapeutics.
The Early Stage Feasibility Study award will support the development of a novel, rapid and high-throughput Lectin based analytical methodology that will be used to further streamline drug development pathways using Glythera’s PermaCarb™ technology platform.
Glythera has previously demonstrated that direct substitution of naturally occurring glycans with its PermaCarb™ platform has the potential to improve drug bioavailability whilst also correcting potentially immunogenic non-human glycosylation profiles. This approach has broad applications in drug discovery, development and production, especially in the high-value biobetter & biosimilar markets.
The project aims to demonstrate the feasibility of using novel, selective recombinant prokaryotic lectins (RPLs) to develop a companion assay to monitor and characterise specific biotherapeutic glycosylation profiles in a high throughput, low cost manner. GlycoSeLect has previously developed a series of glycan selective RPLs and demonstrated applicability for the characterisation, purification and manufacturing of biotherapeutics. Transition to a rapid analytical methodology will add further intensification to Glythera’s existing manufacturing processes, allowing rapid characterisation of drug intermediates as well as the final product.
For more information go to glythera.com/news-events/press-release
26 November 2014
Difficult business requires investment in the right infrastructure and skilled people, as well as developing the right processes for efficient and profitable manufacturing.
At BioProcessUK’s recent meeting in Liverpool, Steve Bates, CEO of the BioIndustry Association (BIA), the trade body for bioscience companies in the U.K., explained how valuable biologics and vaccine manufacturing is to the country, by stating: “The U.K. medicines manufacturing industry, which includes biologics is one of our leading manufacturing sectors; worth £22 billion in exports, generating a trade surplus of £4.9 billion in 2012, and Gross Value Added per head of £149 thousand, significantly higher than any other industry.”
However, manufacturing biologics and advanced therapies is not an easy business as it requires investment in the right infrastructure and skilled people, as well as developing the right processes for efficient and profitable manufacturing.
Eli Lilly is just one of the major pharmaceutical companies that has invested in the U.K. and has built considerable manufacturing expertise in Speke near Liverpool. Peter Whyment, a consultant scientist at Eli Lilly with many years’ scale-up experience, described the issues facing process development scientists and showed a table that Lilly uses to pinpoint where biologic product-related impurities could be introduced and where they can be controlled.
“Down time and clunky processes are your enemy in biologics manufacturing,” commented Whyment.” His advice on scaleup was simple: “Go up in steps of no more that 10x scaleup at a time, if the models are available. Build it layer by layer like an onion with lab to pilot and then manufacture.”
He cited an example of a protein refolding reaction in which a 20 L beaker was used as a model for 5,600 L mixing tank, a 300 fold scaleup. In the mixing tank, a foam was produced, which was not seen in the beaker model, a problem which was remedied by putting a tube down the side of the tank before going into the 8,000 L manufacturing scale tank. Whyment concluded: “Often if you go for a 300-fold scaleup it will rarely work out well, as this example shows the poor yields of the final product caused by the foam were not been seen in the beaker model. He added: “GMP manufacturing is still quite an unpredictable business.”
Whyment detailed how process expertise is transferred and developed at Lilly by describing their training program whereby new staff have to work in process development, product support, and tech transfer departments because he stated: “this helps young scientists that are more lab research minded to understand what to do for the best outcomes and to understand the stuff that simply won’t fly in scale-up.”
The Right Chemistry
Among the advanced therapies showcased at BioProcessUK, where getting the manufacturing right is key to drug safety and profitability were antibody drug conjugates (ADCs). Dave Simpson, Ph.D., CEO of ADC development biotech, Glythera, noted: “In 2014, the first patient in the U.K. was treated with the ADC, Adcetris for non-Hodgkin’s’ lymphoma. After 12 weeks his 76 tumors were gone and he was disease free so ADCs are game-changing drugs. So much so that in 2014 there were 40 distinct ADCs in clinical trials and by July 2014 there were 219 clinical trials with several large pharmas signing up to gain access to novel linkers and toxin payloads.”
However, because ADCs consist of an antibody, a linker, and a highly potent toxic drug, manufacturing them can be complicated. Dr. Simpson explained: “Originally the challenge with ADCs was to bolt on something that was sufficiently toxic. Then when we got that right, the linker stability became a problem and it meant the toxic payload was not always delivered to the right target.”
To get around this stability challenge, Dr. Simpson discussed a cysteine-specific conjugation linker called Permalink™, developed by Glythera. He presented data on trastuzumab/MMAE (monomethyl auristatin E) based ADCs that showed the addition of Permalink generated stable ADCs and resulted in enhanced anticancer activity in cell-based assays, as well as a xenograft model.
Even when the antibody, linker, drug combination is stable, manufacturing ADCs can bring considerable bioprocessing challenges. According to Dr. Simpson, “Today, the linkers and molecules are already out there, so ‘there is no secret ingredient’ and our challenges today are bioprocess ones as manufacturing brings in a chemistry arm to the process.”
Jon Dempsey, Ph.D., head of process introduction at contract development and manufacturing company, Piramal Healthcare, agreed, stating: “With ADCs, as the payloads have become more toxic and potent they have become more difficult to manufacture. The problem is trying to marry the chemical and biochemical needs of the final molecule. Sometimes, for example, adding a linker to the purified antibody causes aggregation that requires chromatographic purification and reformulation with an excipient. This solves the problem but adds in extra costs. Additionally, with ADCs often the toxic drug part is in a solvent that has to be removed but the difficulty is if this is done in single-use plastic purification platforms, there can be leeching from the plastics.”
Dr. Dempsey detailed how manufacturing ADCs requires a full DoE (Design of Experiments), which includes testing Drug Antibody Ratio (DAR), reducing agents and temperature of conjugation. According to Dr. Dempsey finding the correct DAR is vital to maximize loading of tangential flow filtration (TFF) filters and also adding too much of the drug can lead to disposal problems. “Developing the correct conjugation protocol for ADCs is critical to getting the balance of efficacy, toxicity, and cost-effective manufacturing. When this is achieved routinely, then ADCs will become a much more accepted class of medicine.”
Beyond Small-Scale T-Flasks
Cell therapies were discussed as another class of therapy where developing robust manufacturing processes is crucial for decreasing the cost of good and delivering efficacious products. Stephen Ward, Ph.D., COO of the Cell Therapy Catapult, which assists in developing and commercializing cell therapies, said: “The U.K. has a reasonable slice of the cell therapy market because the industry is maturing here. It is no longer about post-docs scraping cells from T-flasks into 6 well plates, now it has some industrial manufacturing capability behind it. To continue this, we need to call on all the expertise from vaccine and biologics manufacturing and apply some of that to cell therapy to enable the production of these expensive therapies to be profitable.”
One company that is demonstrating this expertise is ReNeuron, a firm developing allogeneic cell therapies (CTX), including a neural stem cell line to treat a number of indications, with the furthest advanced being the use of CTX to address the damage caused post-stroke. According to Sharon Grimster at ReNeuron in 2011 in their PISCES (Pilot Investigation of Stem Cells in Stroke) study, 20 million cells/vial were produced and the cells had to be used within days to be effective. Since then the firm has developed a cryopreserved formulation that has a shelf life of three months, as well as a robust manufacturing process by collaborating with companies and academic partners including the Cell Therapy Catapult, Loughborough University, PharmaCell, and Roslin Cells. Grimster stated: “We began collaborating with different partners via the Cell Therapy Catapult in 2013 to use QBD (Quality by Design) principles to deliver a process that would establish the CQAs (Critical Quality Attributes), which would then further enable the automation of our scaled-up process.”
In 2015, ReNeuron’s manufacturing is relocating to Wales where at the Pencoed ATMP facility the firm will use manufacturing-scale automation to produce larger batches of cells in T flasks. Grimster commented: “This work has required a significant amount of process optimization. Next year when we’re validating our process in the facility in Wales we will have security over the supply chain and this is a key asset. Going forward automation and cryopreservation will make this process cost-effective and means our cell therapy will be a good commercial product.”
Grimster added: “twenty two years ago when I was scaling up EPO production I used the same type of robot we’re now using to automate large scale production of our cell therapy, which shows how some of the processes we’ve learned from biologics manufacturing can be transferable to cell therapy production.”
Grimster concluded: “Getting to this stage has been a collaborative effort bringing together all the best cell therapy teams in the U.K. The MHRA has also been very supportive as they are of cell therapy as a whole so our next steps are commercialization and putting in place a global distribution strategy for our cell therapy.”
To ensure the U.K is concentrating its efforts on improving manufacturing of biologics and advanced therapies, a number of initiatives are being put in place. These include the Medicines Manufacturing Industry Partnership (MMIP), which was established in September 2014 by the Association of the British Pharmaceutical Industry (ABPI) and the BIA. Many pharma and biotech organizations are involved in the partnership including: Actavis, AstraZeneca, Eisai, FUJIFILM Diosynth Biotechnologies, GlaxoSmithKline, Oxford BioMedica, and Pfizer. Additionally, Cell Therapy Catapult just announced that it will build a £55 million cell therapy manufacturing center in Stevenage, U.K.
Speakers at BioProcessUK agreed that manufacturing of biologics and advanced therapies should continue to receive government investment if the U.K. is to play an active role in the global biopharm market. Dr Ward echoed these sentiments, when he stated: “For manufacturing effectively, you need the holy trinity of discovery science, manufacturing science and GMP manufacturing if you lose one of these all the other parts will go in the U.K., which is why we have to continue bolster our GMP manufacturing capabilities here.”
Take a look at www.genengnews.com
27 Nov 2014
IP Group plc (LSE: IPO) ("IP Group" or “the Group” or “the Company”), the developer of intellectual property based businesses, is delighted to note that Modern Biosciences plc (“Modern Biosciences” or “MBS”) has entered into an R&D alliance and global option and licence agreement with Janssen Biotech, Inc (“Janssen”) in relation to MBS’ novel bone-protective compounds for the treatment of rheumatoid arthritis (“RA”). The goal of the collaboration, facilitated by the Johnson & Johnson Innovation Centre in London, is to develop new drugs for the treatment of RA.
Under the terms of the exclusive agreement, Modern Biosciences will receive an up-front payment and is eligible to receive development, regulatory and commercialisation milestone payments up to a potential total of £176 million. In addition, MBS will receive royalties on future sales of any products that may result from the alliance upon successful launch and commercialisation.
RA is a severe, painful inflammatory disease that can cause progressive joint and bone erosion and eventually lead to disability. MBS’ compounds work by a novel mechanism of action that targets both the inflammatory component of RA and the associated bone destruction. This approach has the potential to not only protect the joints of people living with RA from further damage but to control the pain and swelling associated with the disease. The most advanced of MBS’ compounds is currently in pre-clinical development and is due to enter Phase 1 clinical studies in 2015.
For more information, please contact: IP Group plc http://www.ipgroupplc.com
14th July, 2016
Avacta Group plc (AIM: AVCT) (“Avacta” or “the Group”) the developer of Affimer® biotherapeutics and research reagents and Glythera Limited the developer of advanced, stable conjugation chemistries and novel, ultra-potent toxin payloads, today announce that they have established a collaboration to evaluate the use of Glythera’s PermaLink™ conjugation chemistry in combination with Avacta’s Affimer technology with the aim of developing a new class of highly targeted bio-therapeutics as a superior alternative to the established class of antibody drug conjugates (ADCs).
ADCs use an antibody to which a toxin/chemotherapy payload is chemically attached for targeted delivery to a tumour. Over 50 ADCs are currently in clinical development; of these, approximately a quarter are in Phase II or Phase III. The market is estimated to be worth around $1bn today from two approved compounds and is expected to be worth $10bn annually by 2024.
The combined potential benefits of the Affimer and PermaLink technologies have the potential to create an analogous leading protein drug conjugate platform with a number of benefits over current ADC offerings. Use of Avacta’s Affimer technology (i) provides the ability to closely control the position and number of toxins in the payload; (ii) has the benefit of much shorter development times (iii) has the flexibility to “design-in” the required pharmacokinetics (the time the drug spends in the blood stream), and (iv) is much easier, more consistent and has lower cost production. The small size of the Affimer molecule is likely to also improve tumour penetration compared with antibodies which are ten times larger in size.
Another major issue facing ADCs is the limited stability of chemical linkages currently used to attach the toxin to the antibody resulting in the toxin coming off the antibody and causing “off-target” and often severe, side effects. Glythera’s PermaLink chemical linkers provide much more stable attachment of the toxin/chemotherapy and can potentially reduce such off-target toxicity effects.
Under the terms of the agreement, the companies will develop materials and methods to be used in the generation of Affimer-drug conjugates. The proof of concept study aims to demonstrate the key technical and commercial benefits of the combination over traditional antibody and linker approaches. The two companies will partner to offer Affimer-drug conjugate development services, and licensing of the combined platform, to pharmaceutical developers.
Dr Alastair Smith, Chief Executive Officer, Avacta, commented:
“At the half year we set out a detailed commercial strategy for Affimer reagents and therapeutics. We highlighted the importance of commercial partnerships in order to make rapid progress in the areas of strategic focus. In that context we recently announced a collaboration with Mologic to develop Affimer based lateral flow devices which would open up the rapid diagnostics market opportunity and today we are very pleased to report the establishment of this collaboration with Glythera in the area of ADCs, another important application area for Affimer technology.
Avacta’s Affimer technology has significant benefits for drug conjugate development, and the combination of the two companies’ technologies has the potential to deliver a best-in-class solution for those wishing to access such a platform. We are therefore confident that this partnership with Glythera will further demonstrate the utility of the Affimer platform as a powerful approach to generating a broad range of biotherapeutics, creating opportunities for third party licensing of the platform with the potential to generate long-term value for both companies.
We continue to make good progress across all aspects of the strategy that we set out and I look forward to further updating the market in due course.”
Dr Dave Simpson, Chief Executive Officer, Glythera, said:
“Combining Glythera’s PermaLink conjugation chemistry with Avacta’s Affimer technology will demonstrate the benefits of PermaLink across a new targeting molecule class, opening additional avenues for bringing novel therapeutic assets to market. This is an exciting step forward in bio-therapeutic development, and could lead to improved patient outcomes.”
20th February 2017
Glythera demonstrates improved activity and safety of PermaLink®-based ADCs
Appoints Scientific Advisory Board
-Significantly improved tolerability of ADCs incorporating highly potent toxins-
- Efficacy outperforms industry-standard ADC technology –
-Development of proprietary ADC pipeline supported by key industry appointments to SAB-
Glythera Limited (‘Glythera’), the next generation Antibody Drug Conjugate (‘ADC’) development company, today provides further evidence that PermaLink®, its proprietary non-maleimide conjugation platform, enables the production of ADCs with potentially greater clinical utility than current industry-standard conjugation technologies.
ADCs are rapidly gaining ground as an important tool in the fight against cancer by specifically delivering highly potent toxins to tumour cells and limiting damage to healthy tissues. However, clinical utility depends on the stability of the conjugation chemistry; the current industry-standard maleimide approach is prone to the premature release of toxic payloads, thus limiting the dose that can be administered safely to patients and, subsequently, reducing ADC therapeutic index. Glythera’s PermaLink® is an alternative conjugation chemistry platform with greater stability and delivery metrics.
In recent in vivo studies, PermaLink®-based ADCs, have been shown to provide a near 100% improvement in tolerability when compared with equivalent maleimide-based ADCs, as well as enhanced tumour-cell killing and an overall improvement in tumour response in xenograft models. This combination of improved tolerability and efficacy of PermaLink® based ADCs will enable the safer use of higher-potency toxins for enhanced therapeutic utility.
Glythera is developing a portfolio of next-generation PermaLink® ADCs, focused on difficult-to-treat cancers. These combine unique high-potency toxins with novel antibodies. The Company is assessing and developing a broad range of innovative, highly potent toxin payloads from numerous toxin classes - including known and new mechanisms. In addition, Glythera is collaborating with its partners to evaluate a range of clinically important antibody targets and intends to identify its first clinical candidate before the end of 2018.
In another significant step, Glythera has appointed a Scientific Advisory Board to support and advance the Company’s industry-leading ADC development pipeline, with its first appointments being Dr Morris Rosenberg and Dr Robert Lutz. Dr Rosenberg has over 15 years in the ADC field, most notably as Vice President of Process Sciences at Seattle Genetics Inc., whilst Dr Lutz spent 23 years with Immunogen Inc., culminating in his role as Vice President of Translation Research and Development. Glythera hopes to announce further key appointments to its SAB in due course.
Dr Robert Lutz commented: “The PermaLink® conjugation technology provides a highly selective and safe alternative to the current maleimide chemistries, whilst reducing the significant risk associated with de-drugging of potent toxins and adverse events in the clinic.”
Dr Morris Rosenberg added: “Glythera has accessed an impressive range of novel approaches to on-market toxins which meets the industry’s current need for ADCs that can address difficult-to-treat solid tumours with highly potent toxin payloads.”
Dr Dave Simpson, CEO of Glythera, said: “Glythera continues to add significant value to the ADC field, not only by improving the safety and efficacy of ADC targets in its partners development pipelines, but by accessing highly potent toxins and clinically important monoclonal antibodies for the development of our own next-generation ADC portfolio focused on improving the lives of patients living with difficult-to-treat cancers.”