Summit Therapeutics Reports 4th Quarter and Year End Financial Results and Operational Progress

Accessibility: Skip TopNav

March 29, 2017 07:00 ET

Summit Therapeutics plc

Summit Therapeutics plc

Summit Therapeutics plc

('Summit', the 'Company' or the 'Group')

SUMMIT THERAPEUTICS REPORTS FINANCIAL RESULTS FOR THE

FOURTH QUARTER AND FISCAL YEAR ENDED 31 JANUARY 2017 AND OPERATIONAL PROGRESS

Conference Call Today at 1:00pm BST / 8:00am EDT

Oxford, UK, 29 March 2017 - Summit Therapeutics plc (AIM: SUMM, NASDAQ: SMMT), the drug discovery and development company advancing therapies for Duchenne muscular dystrophy ('DMD') and C. difficile infection ('CDI'), today reports its financial results for the fourth quarter and fiscal year ended 31 January 2017.

Mr Glyn Edwards, Chief Executive Officer of Summit, commented: "We believe the progress made over the past year in our DMD and CDI programmes, combined with our strengthened financial position following the signing of the Sarepta licensing agreement has placed us in a strong position to deliver value for our patients and shareholders.

"Our Phase 2 proof of concept trial, PhaseOut DMD, is well underway with enrolment expected to be completed in the second quarter of 2017. We now look forward to providing the full analysis of 24-week biopsies from the approximately 20 patients dosed with the F3 or F6 formulation of ezutromid, plus 24-week MRI and functional measures from all patients in the trial, in the first quarter of 2018. This approach is in lieu of reporting interim analysis from a smaller group in 2017, and it is expected to provide a more complete picture of the potential benefits of ezutromid at this time point on utrophin expression, muscle health and muscle function.

"In CDI, our Phase 2 clinical data supports the potential front-line use of ridinilazole to treat the initial infection and provide patients with a sustained clinical response. This sustained clinical response is the focus of our planned Phase 3 programme that is designed, with input from the FDA and EMA, to evaluate superiority of ridinilazole over the current standard of care antibiotic vancomycin. With the Phase 3 trials planned to start in the first half of 2018, we look forward to an exciting and important time ahead as we seek to bring these two potentially important treatment options one step closer to patients."

Utrophin Modulation Programme for DMD

Exclusive Licence and Collaboration Agreement

Summit granted Sarepta Therapeutics Inc., exclusive European rights to utrophin modulator pipeline including ezutromid

Summit received $40 million upfront payment and is eligible to receive up to $522 million in future ezutromid-related milestones, plus sales royalties

Global research and development costs related to ezutromid and utrophin modulator pipeline to be split 55%/45% (Summit/Sarepta) starting in 2018

Ezutromid (formerly SMT C1100) Highlights

PhaseOut DMD Phase 2 clinical trial ongoing in UK and US, with enrolment expected to finish in Q2 2017

Analysis of full 24-week biopsy, MRI and functional data from PhaseOut DMD expected to be reported Q1 2018 in lieu of an interim 24-week biopsy analysis from an initial group of patients

Independent Data Monitoring Committee supported the extension of PhaseOut DMD following interim review of safety and tolerability data

F6 formulation of ezutromid achieved six-fold increase in maximum plasma levels in DMD patients compared to F3 formulation and is being evaluated in PhaseOut DMD clinical trial

Ezutromid received Fast Track designation and Rare Pediatric Disease designation from the US Food and Drug Administration

Publication on the development of biomarkers to quantify utrophin protein and muscle fibre regeneration demonstrating continued thought leadership on utrophin modulation

Ridinilazole (formerly SMT19969) Highlights

End of Phase 2 regulatory meetings with US and European regulators assisted design of Phase 3 development programme for ridinilazole

Ongoing activities to prepare ridinilazole for Phase 3 clinical trials which are planned to start in H1 2018

Further data from Phase 2 CoDIFy clinical trial showed ridinilazole outperformed standard of care antibiotic vancomycin in preserving microbiome during treatment of CDI

Treatment completed in exploratory Phase 2 clinical trial evaluating ridinilazole against fidaxomicin with top-line data expected to be reported in Q2 2017

Grant of key patent by the US Patent and Trademark Office strengthens patent estate protecting ridinilazole

R&D organisation strengthened by appointing industry leader, Dr David Roblin, as Chief Operating Officer and President of Research and Development; full-time role commences June 2017

Financial Highlights

Cash and cash equivalents at 31 January 2017 of £28.1 million compared to £16.3 million at 31 January 2016

Loss for the year ended 31 January 2017 of £21.4 million compared to a loss of £20.1 million for the year ended 31 January 2016

Conference Call and Webcast Information

Summit will host a conference call and webcast to review the financial results for the fiscal year ended 31 January 2017 today at 1:00pm BST / 8:00am EDT. To participate in the conference call, please dial +44 (0)20 7136 2050 (UK and international participants) or +1 646 254 3361 (US local number) and use the conference confirmation code 1859782. Investors may also access a live audio webcast of the call via the investors section of the Company's website, www.summitplc.com. A replay of the webcast will be available shortly after the presentation finishes.

About Summit Therapeutics

Summit is a biopharmaceutical company focused on the discovery, development and commercialisation of novel medicines for indications for which there are no existing or only inadequate therapies. Summit is conducting clinical programmes focused on the genetic disease Duchenne muscular dystrophy and the infectious disease C. difficile infection. Further information is available at www.summitplc.com and Summit can be followed on Twitter (@summitplc).

For more information, please contact:

Forward Looking Statements

Any statements in this press release about our future expectations, plans and prospects, including statements about development and potential commercialisation of our product candidates, the therapeutic potential of our product candidates, the timing of initiation, completion and availability of data from clinical trials, the potential benefits and future operation of the collaboration with Sarepta Therapeutics Inc., including any potential future payments thereunder, any other potential third-party collaborations and expectations regarding the sufficiency of our cash balance to fund operating expenses and capital expenditures, and other statements containing the words "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "plan," "potential," "predict," "project," "should," "target," "would," and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: the uncertainties inherent in the initiation of future clinical trials, availability and timing of data from ongoing and future clinical trials and the results of such trials, whether preliminary results from a clinical trial will be predictive of the final results of that trial or whether results of early clinical trials will be indicative of the results of later clinical trials, expectations for regulatory approvals, availability of funding sufficient for our foreseeable and unforeseeable operating expenses and capital expenditure requirements and other factors discussed in the "Risk Factors" section of filings that we make with the Securities and Exchange Commission, including our Annual Report on Form 20-F for the fiscal year ended 31 January 2016. In addition, any forward-looking statements included in this press release represent our views only as of the date of this release and should not be relied upon as representing our views as of any subsequent date. We specifically disclaim any obligation to update any forward-looking statements included in this press release.

CHAIRMAN'S STATEMENT

The past year has been one of strong progress across the Company as we continue to advance our innovative drug programmes targeting rare and infectious diseases. Our focus in rare diseases is on our utrophin modulator pipeline for the treatment of the fatal muscle wasting disease, Duchenne muscular dystrophy ('DMD'). In infectious diseases, we are developing a novel antibiotic called ridinilazole for the treatment of patients with infections caused by the bacteria C. difficile.

A major highlight of the year was the signing of a licence and collaboration agreement with Sarepta Therapeutics Inc. ('Sarepta') for European rights to our utrophin modulator pipeline. This agreement provided a $40 million upfront cash payment to Summit with the potential for substantial future success based milestone and royalty payments. The year also included positive clinical data in both our DMD and CDI programmes as we continue to progress these innovative therapies through clinical trials and towards potential commercialisation.

This progress leaves us poised for an exciting year ahead. This is expected to include the continuation of our Phase 2 proof of concept trial for our lead utrophin modulator, ezutromid, and activities to prepare our novel antibiotic ridinilazole to be ready to enter Phase 3 clinical trials in the first half of 2018.

A Balanced Portfolio

I believe our pipeline of investigational therapies provides a balanced risk profile. Our DMD programme aims to address the underlying cause of the disease by seeking to maintain production of utrophin protein to compensate for the dystrophin that is lacking in individuals with DMD, in order to maintain healthy muscle function. We have shown the potential of this therapeutic approach in preclinical disease models and our focus is on demonstrating proof of concept in patients with DMD for ezutromid in the ongoing Phase 2 clinical trial called PhaseOut DMD. Generation of positive clinical data would clear a key technical milestone and support the continued development of ezutromid as a potential disease modifying treatment for this devastating muscle wasting disease.

To complement this, our novel class antibiotic ridinilazole has already shown evidence of clinical efficacy in patients with CDI in our Phase 2 clinical trial. In my view, this leaves ridinilazole in a strong position to continue to progress to Phase 3 clinical development and towards potential regulatory approval, particularly in light of the historic clinical success of antibiotics that have generated positive Phase 2 data.

Operational Progress: Sarepta Therapeutics Licence and Collaboration Agreement

A major achievement of the past year was signing the licence and collaboration agreement with Sarepta. This agreement granted Sarepta exclusive commercial rights in Europe, Turkey and the Commonwealth of Independent States to our utrophin modulator pipeline, including our Phase 2 candidate ezutromid. In exchange, we benefited from a cash injection of $40 million with the potential for additional development, regulatory and sales milestones that for ezutromid alone total up to $522 million, plus future sales royalties.

This deal brings to Summit a number of benefits. It provides access to additional development and regulatory expertise from Sarepta to support ezutromid and our wider utrophin pipeline while, importantly, we retained full commercial rights in other territories including the United States.

Operational Progress: R&D overview

It is an important time ahead for both programmes. In DMD, we expect to conclude enrolment into PhaseOut DMD. This clinical trial is the first long-term study conducted with a utrophin modulator, and aims to demonstrate proof of concept for ezutromid in patients with DMD. Proof of concept would represent a major technical milestone for our utrophin modulation programme and we look forward to reporting the full 24-week data from this trial in the first quarter of 2018.

In parallel, we continue to develop our earlier stage pipeline of future generation utrophin modulators. This pipeline shows our deep commitment to developing effective therapies for the DMD community. I look forward to reporting on the continued advance of this pipeline which is being developed as part of our strategic alliance with the University of Oxford as we seek to maintain our leadership position in the field of utrophin modulation.

There is an urgent need to develop new antibiotics to combat the serious healthcare threat posed by pathogens, including C. difficile. We continue to believe that ridinilazole offers the potential to change the treatment paradigm in CDI. Further data we presented from our proof of concept Phase 2 trial showed ridinilazole was highly preserving of the gut microbiome in patients during treatment. This observation was in stark contrast to patients treated with the current standard of care antibiotic vancomycin whose microbiomes were severely damaged during treatment. A damaged microbiome leaves patients at high risk from disease recurrence. We therefore believe ridinilazole has the potential to be positioned as the mainstay treatment for CDI due to its potential to treat initial infection and reduce rates of recurrence.

Future Development Strategy

Our strategy for the future development of both programmes remains clear. In DMD, if any of our utrophin modulators receive marketing approval, we remain committed to independently commercialising them in the United States, one of the world's most important pharmaceutical markets. Commercialisation options for the other territories not covered by the licence and collaboration agreement with Sarepta continue to be evaluated.

As ridinilazole is prepared for entry into Phase 3 clinical trials, we are in parallel evaluating various options to support its future development as we seek to maximise the value of this exciting asset. This includes a collaboration agreement with a third party, or securing substantial non-dilutive funding from government entities or not for profit organisations. This evaluation will consider a number of factors as we seek to identify the optimal path to continue the development of ridinilazole.

To support the ongoing development of the two programmes, the team was further strengthened during the year. This was highlighted by the full-time appointment of Dr David Roblin as our Chief Operating Officer and President of Research and Development. David has had an extensive and highly successful career in the pharmaceutical industry that included holding senior management roles at Pfizer and Bayer. Most recently, David led the establishment of operations at the Francis Crick Institute in London as Chief Operating Officer. David's broad expertise across all stages of drug development in many different therapeutic areas, including infectious diseases, will be invaluable to the wider team at Summit. David has been acting as a research and development adviser to Summit since 2014, and we look forward to working with him as part of the Summit team in this role on a part-time basis starting in April 2017 before moving to full-time in June 2017. For Summit to have attracted an individual of David's calibre and reputation is a reflection of the promise and innovation in our DMD and CDI programmes.

Summit has made strong progress with the programmes and the development of the business in 2016 and we look forward to an exciting year ahead. We will continue with our proof of concept trial for ezutromid while activities to prepare ridinilazole for Phase 3 clinical trials continue.

I would like to thank all of our shareholders for their continued support. I also wish to sincerely thank all the patients and their families who are involved with our clinical trials. Without their dedication and support, we would not be able to advance these potential new treatments. Finally I would like to thank the team at Summit for the continued hard work over the past 12 months as we seek to advance potential new medicines that have the opportunity to transform the lives of patients and their families.

Frank Armstrong, FRCPE, FFPM

Non-Executive Chairman

Summit is a biopharmaceutical company focused on the discovery, development and commercialisation of novel medicines for indications in rare diseases and infectious diseases for which there are no existing or only inadequate therapies. In rare diseases, Summit is seeking to develop a treatment for all patients affected with the fatal disorder DMD using its utrophin modulation technology. Summit's focus in infectious diseases is on advancing the development of an antibiotic called ridinilazole that has the potential to not only treat the initial CDI infection, but importantly to reduce rates of disease recurrence.

Duchenne Muscular Dystrophy: Utrophin Modulation Programme

DMD is the most common and most severe form of muscular dystrophy. There are approximately 50,000 patients with DMD in the developed world. The disease predominately affects males and results in the progressive wasting of muscles throughout the body. DMD typically results in death by the time patients reach their late twenties.

Patients with DMD are unable to produce dystrophin, a protein essential for maintaining healthy muscle function. Utrophin is a naturally occurring protein that is functionally and structurally similar to dystrophin, and plays an active role in the development of new muscle fibres, both in foetal development and in the repair of damaged muscle fibres. Utrophin production is switched off in mature muscle fibres, and in the case of a healthy individual, replaced by the production of dystrophin. Utrophin modulation has the potential to maintain the production of utrophin in all skeletal muscles, including the diaphragm and the heart, to compensate for the lack of dystrophin in patients with DMD and so restore and maintain healthy muscle function. A key benefit of utrophin modulation is that it is independent of the underlying genetic fault in the dystrophin gene and therefore has the potential to treat the entire patient population.

Summit has established a leadership position in the field of utrophin modulation and is developing a pipeline of small molecule utrophin modulator therapies, including ezutromid which is being evaluated in a Phase 2 clinical trial.

Exclusive Licence and Collaboration Agreement with Sarepta Therapeutics Inc. ('Sarepta')

In October 2016, Summit announced a licence and collaboration agreement with Sarepta. This granted Sarepta exclusive commercial rights to the Company's utrophin modulator pipeline, including ezutromid, in Europe, Turkey and the Commonwealth of Independent States, with an option over specific countries in Central and South America. Summit retains commercialisation rights in all other countries, including the US and Japan.

Under the agreement, Summit has agreed to collaborate with Sarepta on the research and development of utrophin modulator therapies under a joint, global development plan. This agreement also provides Summit with access to Sarepta's development, regulatory and commercialisation expertise to support the continuing development of Summit's utrophin modulator pipeline.

Financially, Summit received an upfront payment of $40 million, and will be eligible for future ezutromid-related development, regulatory and sales milestone payments totalling up to $522 million. This includes a $22 million milestone, payable on or after 1 April 2017, upon the first dosing of the last patient in Summit's ongoing PhaseOut DMD trial. In addition, Summit is eligible for escalating royalties ranging from a low to high teens percentage of net sales in the licensed territories.

Summit will also be eligible to receive development and regulatory milestones related to potential future generation utrophin modulator candidate(s). Beginning in 2018, Summit and Sarepta will share at a 55%/45% split specified global research and development costs related to Summit's utrophin modulator pipeline, including ezutromid and its future generation utrophin modulator candidate(s).

Ezutromid Clinical Trial Activities

Ezutromid: Phase 2 Proof of Concept Trial

PhaseOut DMD is a Phase 2 clinical trial evaluating ezutromid in patients with DMD. This 48-week open-label trial is ongoing in the UK and the US and aims to establish proof of concept for ezutromid through the evaluation of muscle structure and health. Enrolment of approximately 40 patients is ongoing for the two formulations of ezutromid being tested, F3 and, more recently F6, and Summit expects to complete trial enrolment in the second quarter of 2017.

DMD is characterised by high levels of muscle degeneration caused by the absence of functional dystrophin. Muscle fibres consequently enter into a cycle of repair and degeneration that over time leads to fat infiltrating into muscle and loss of ambulation and other functional abilities. Ezutromid aims to maintain production of utrophin so that it can substitute for the missing dystrophin. This has potential to allow muscle fibres to mature and so reduce the level of muscle degeneration, reduce the rate of fat infiltration and reduce the rate of decline in functional abilities. PhaseOut DMD is assessing all of these factors through various techniques including use of muscle biopsy to evaluate utrophin distribution and muscle fibre regeneration and maturity; magnetic resonance imaging to measure fat infiltration; and various functional tests including the North Star Ambulatory Assessment and the six minute walk test.

The Company expects to report full analysis of the 24-week biopsy data in the first quarter of 2018, in lieu of reporting an earlier interim 24-week biopsy analysis from a smaller group of these patients in 2017. The full analysis group consists of approximately 20 samples from patients dosed with both the F3 or F6 formulations of ezutromid who will provide a 24-week biopsy sample. The Company plans to analyse all 24-week treatment biopsies once all samples have been collected. In addition to reporting on the full 24-week biopsy data, Summit expects to announce the 24-week analysis of MRI and functional data from all patients in the trial. The Company believes that this revised approach of analysing a larger dataset will provide a more complete picture of ezutromid's potential by evaluating a larger number of patients.

In addition to PhaseOut DMD, Summit plans to conduct a randomised, placebo controlled trial designed with the potential to support accelerated and conditional approvals in the US and Europe, respectively. It is anticipated that this trial would start after positive interim data from PhaseOut DMD, and the Company would plan to provide timing guidance following the release of the 24-week dataset.

In March 2017, Summit applied to the MHRA and FDA regulatory authorities to extend PhaseOut DMD as the Company seeks to allow for the transition of patients participating in PhaseOut DMD onto an open-label extension at the end of the initial 48 weeks of the trial without a cessation in dosing. This decision followed support for the Company's plan from the trial's independent Data Monitoring Committee upon an interim review of the safety and tolerability data from the ongoing trial. The extension phase is expected to last until ezutromid either receives marketing approval in relevant countries or its development is discontinued.

Ezutromid: Phase 1 New Formulation Trial

Summit announced in August 2016 results from a Phase 1 clinical trial that showed a new formulation of ezutromid called F6 achieved a substantial increase in plasma exposure in patients compared to the current clinical formulation called F3. At the highest dose of F6 (1,000 mg, twice daily), the five evaluable patients achieved a six-fold increase in average maximum plasma levels compared to the highest dose of formulation F3 (2,500 mg, twice daily).

Summit is evaluating the safety and efficacy of F6 alongside F3 in the ongoing PhaseOut DMD clinical trial. It is anticipated that approximately ten patients enrolled at trial sites in the US will be dosed with F6. We believe both formulations of ezutromid have the potential to modulate the expression of utrophin, and the inclusion of F6 is expected to provide a greater understanding of the potential relationship between ezutromid drug exposure and clinical benefit.

Pipeline and Research Activities

Future Generation Utrophin Modulators

As part of the Company's strategy to maintain its leadership position in the field of utrophin modulation, Summit is developing a pipeline of future generation utrophin modulators. This research, conducted as part of the strategic alliance with the University of Oxford, is building on the promise of ezutromid to identify new, structurally distinct molecules, including ones that may have new utrophin related mechanisms.

Summit also has a number of second generation utrophin modulators that are structurally related to ezutromid, but designed to achieve higher drug plasma levels. In September 2016, Summit placed the development of these modulators on hold as the key objective of this development programme was fulfilled by the substantial increase in ezutromid plasma levels achieved by the F6 formulation.

Development of Biomarkers

As highlighted above, a key endpoint in the PhaseOut DMD trial is measurement of utrophin and muscle regeneration biomarkers from muscle biopsies. Summit, in collaboration with Flagship Biosciences Inc. ('Flagship'), has been developing an automated, digital analysis tool to precisely measure muscle maturity and integrity and utrophin expression in individual fibres, and data from this research were presented at the 21st International Congress of the World Muscle Society held in Granada, Spain, in October 2016. The Flagship research builds on a manual quantification approach developed in collaboration by Summit and research groups at the Institute of Child Health at University College London, which was published in the peer reviewed literature in March 2016. The development of these biomarkers represents an important step in helping to further our understanding of the potential benefits of utrophin modulator therapies such as ezutromid.

Fast Track and Rare Pediatric Disease Designations

In September 2016, ezutromid was granted two separate designations by the FDA in the treatment of DMD: Fast Track and Rare Pediatric Disease. Fast Track designation provides the Company with advantages such as opportunities for more frequent interactions with the FDA during all aspects of development, submission of a New Drug Application ('NDA') on a rolling basis, and eligibility for accelerated approval and priority review. Rare Pediatric Disease designation could qualify Summit for a Priority Review Voucher if ezutromid is approved before 1 October 2022. The voucher could be used for a subsequent marketing application or sold or transferred an unlimited number of times (although only used once).

C. difficile Infection Programme

CDI is a major healthcare threat with over one million cases estimated between the United States and Europe each year. Mainstay treatments are dominated by broad spectrum antibiotics, the use of which are associated with high rates of recurrent disease. With each episode typically being more severe and associated with increased risk of mortality, recurrent disease is the key clinical issue in CDI.

Ridinilazole is a novel class antibiotic that has the potential both to treat the initial infection as well as to reduce the high rates of recurrent disease experienced in CDI. Ridinilazole has received Qualified Infectious Disease Product designation and has been granted Fast Track designation in the US.

The development of ridinilazole has been financially supported by Wellcome Trust Seeding Drug Discovery and Translational Awards.

Phase 2 Clinical Programme

Summit has generated a comprehensive package of data supporting ridinilazole as a potential new front-line treatment of CDI. In the Phase 2 proof of concept trial, called CoDIFy, ridinilazole achieved statistical superiority over the current standard of care antibiotic vancomycin in sustained clinical response, including a large numerical reduction in the rate of recurrent disease.