Business Update And Change of Name from Pro Bono Bio

Ascension Healthcare plc

Business Update And Change of Name from Pro Bono Bio

LONDON, January 4, 2019 – Ascension Healthcare plc (“Ascension” or the “Company”), a clinical-stage biopharmaceutical company focused on developing and commercialising innovative therapies for haemophilia and osteoarthritis today provides a business update and announces a Company change of name from Pro Bono Bio.

BUSINESS UPDATE

Haemophilia

• SelectAte Phase II clinical development programme initiated to evaluate the Company’s wholly-owned PEGLip technology in providing prophylactic Factor VIII (FVIII) treatment to haemophilia A (HA) patients with inhibitors to FVIII.  Top-line results are expected during 2019.
• Two pre-clinical programmes initiated to prepare for Phase II clinical trials readiness, targeting (i) prophylactic FVIII treatment of HA patients subcutaneously (SubcutAte programme) and (ii) therapy for patients who, although not currently treated prophylactically, have moderate FVIII deficiency (ChapAte programme).

Commenting on the Haemophilia products in development, Professor Edward Tuddenham , emeritus Professor of Haemophilia at University College London, commented:

“The clinical trials of Ascension’s PEGylated liposomes in conjunction with replacement blood factor VIII revives an established, but neglected approach to enhancing the in vivo properties of factor VIII. These include an extended half-life, alternative route of administration and protection from inhibitory anti-body.  This application of a simple, affordable technology, when similar advances are being reported with extensive modification to factor VIII or mimetics are associated with very high cost, has the potential to make haemophilia A therapy universally accessible to all.”

Osteoarthritis

• Ascension successfully increased sales of its wholly-owned commercial gel product “Flexiseq” for osteoarthritis sufferers in the United Kingdom, Ireland and Germany from an enhanced sales and marketing drive. Flexiseq is currently sold over-the-counter in pharmacies and retail outlets including Boots, Lloyds, Superdrug, Tesco, Sainsburys, DM, Rossman, Muller, as well as many independent outlets. Flexiseq is also sold in other European countries and in MENA and South-East Asia and Australasia, through local or regional collaborations or distribution arrangements. The products have been clinically tested in several phase III trials.

CHANGE OF NAME TO ASCENSION HEALTHCARE PLC

Pro Bono Bio plc is now called Ascension Healthcare plc.

JP MORGAN CONFERENCE

Ascension Healthcare plc will be attending the JP Morgan Healthcare Conference in San Francisco from 7 – 10 January 2019 and the management team are available for meetings with investors, analysts and potential partners. Those interested in meeting the Company may contact Consilium on the details below.

For further information please contact:

About Ascension Healthcare plc

Ascension Healthcare plc is a clinical-stage biopharmaceutical company focused on developing and commercialising innovative therapies for the treatment of haemophilia and osteoarthritis.

The Company has three products in clinical or pre-clinical development for the treatment of Haemophilia A and also a range of internationally marketed products for osteoarthritis sufferers.  

For more information please visit: https://ascension.co.uk/

About Haemophilia

The Company’s product development programmes are focused on treating a form of haemophilia, haemophilia A (“ HA ”), a congenital bleeding disorder which leaves a patient at risk of uncontrolled bleeding due to a lack of blood clotting Factor VIII (“ FVIII ”). HA is the most common form of haemophilia, affecting 80% - 85% of the total haemophilia population. HA has a prevalence rate of about 1 in 10,000 births and can be categorised from mild (5-40%) to moderate (1-5%), to severe (<1%) circulating FVIII depending on the actual level of functioning FVIII in the body.

The Company has developed and acquired intellectual property over several years (PEGylated liposomes and PEGylated blood proteins) with the intention of developing novel products for haemophiliacs, principally to deal with:

1. problems relating to the development of inhibitors in severe haemophiliacs - the SelectAte clinical product development programme;
2. the lack of a convenient, safe, effective and economical prophylactic treatment administered by subcutaneous injection for severe haemophiliacs - the SubcutAte pre-clinical product development programme; and
3. the need for a prophylactic treatment to boost existing FVIII levels in moderate and mild HA patients - the ChapAte pre-clinical product development programme.

The Company plans to undertake, under world leading Haemophilia physician guidance, clinical and pre-clinical trials to provide clinical proof of concept data in humans (SelectAte) and clinical readiness to deliver such proof of concept data (SubcutAte and ChapAte).

The Company is developing the following haemophilia programmes (the “ Haemophilia Projects ”):

SelectAte is being developed to treat severe HA patients who have developed inhibitors (neutralising antibodies) to FVIII. Approximately 30% of severe HA patients develop inhibitors to prophylactic FVIII replacement therapy, rendering such therapy ineffective. Current options for these patients are (i) Immune Tolerance Induction Therapy (ITI) to eradicate inhibitors, which is costly, lengthy and sometimes unsuccessful, and unpleasant or (ii) bypassing agents to treat or prevent bleeds on demand or (iii) prophylactically which can be very costly;  some of these agents have an FDA “black box” safety warning (risk of blood clots and death).

This is a large market that is, at present, not served by a safe, convenient, inexpensive prophylactic treatment.

SubcutAte is a FVIII replacement therapy directed at severe HA patients that have not gone on to develop inhibitors that:

1. can be more conveniently and comfortably administered subcutaneously (i.e. under the skin, not through the vein) as a small bolus on a daily basis in contrast to intravenous injection; and
2. will enter the circulation over time, with the aim of achieving a stable circulating level of treated FVIII, in contrast to intravenous administration. Intravenous administration has a “saw-tooth” concentration profile caused by periodic injections where the high doses of initial FVIII levels after dosing are run down (potentially to sub-optimal levels) and are restored by subsequent injections that are wasteful and potentially leaves the patients without cover.

ChapAte is directed at treating mild (5-40% of normal FVIII) and moderate (1-5% of normal FVIII) HA patients on a prophylactic basis. Such patients are usually treated with FVIII on demand and not prophylactically. Mild patients can also be treated with desmopressin on demand that boosts plasma levels of FVIII.  Although technically a more challenging project than SelectAte and SubcutAte, if the proposed clinical trial is successful, ChapAte potentially provides a new prophylaxis for mild to moderate HA patients.

Despite new product introductions and further products in late development, the market opportunity for these product profiles remains substantial.  The treatment market for HA is approximately $8.9bn, of which:

• • $6.6bn is focused on replacement factors. (80% of the market value is concentrated in four players)
  • $2.3bn focused on alternative (bypass) products (concentrated in two major players). 

About Osteoarthritis

Osteoarthritis (‘OA’) is the most common form of joint disease and is estimated to affect up to 20% of the adult population. Prevalence increases with age and comorbidities such as obesity and cardio-vascular disease are common. It has a huge economic cost on society made up from treatment costs, surgery and a host of indirect costs such as reduced productivity/loss of work, decreased independence and need for care.

The origin and advance of OA are believed to be caused by a mix of mechanical, structural, genetic and environmental factors. There is currently no cure for the disease and for many the end result is total joint replacement with all its costs and limitations. The standard treatment protocol for the symptoms starts with non-pharmacological interventions beginning with patient education, exercise and weight loss. Pain and inflammation are treated with common painkillers (aspirin, paracetamol (acetaminophen) and Non-Steroidal Anti-Inflammatory Drugs (NSAIDS, such as diclofenac, ibuprofen and naproxen).  A 2016 study published in the Lancet (da Costa et al.) concluded that paracetamol is ineffective for the treatment of OA. Those receiving poor relief or who cannot tolerate NSAIDs may be given opioids (codeine, etc.).

Whilst these products provide some temporary symptomatic relief, they do so with serious safety issues that are increasingly well recognised. The over-the-counter nature of some NSAIDs means that their use is poorly controlled and the risks of combining two or more NSAIDs are poorly understood by patients. This is despite the recognition of their potential to interact with anti-hypertension drugs such as diuretics and ACE inhibitors, negating their effect and their association with gastro-intestinal and cardio vascular problems, in particular. The use of NSAIDs even in low doses for short periods has been linked to serious cardio-vascular adverse events, and therefore their use is cautioned against in patients with histories of heart disease.

In reality, there has been almost no significant advance in OA treatments since the development of ibuprofen and diclofenac in the 1970s, although the value of products with improved safety profiles was briefly shown by the initial growth of market for the putatively safer COX2 product to over £6bn between 1999 and 2004, before they too exhibited serious cardio-vascular side effects.

As a result, there is a large population of patients for whom pharmaceutical treatments are ineffective, unsuitable or unattractive. These patients may also resort to alternatives such as supplements (glucosamine and chondroitin), which still lack good clinical evidence, or invasive procedures such as the intra-articular injection of hyaluronic acid.

Overall, the patient population is poorly served for the simple, convenient treatment of this chronic condition. These are the patients now being helped by FLEXISEQ which offers a number of unique benefits to fill the unmet need for effective and safe treatment.

FLEXISEQ is:

Clinically proven to be as effective as an oral prescription pain killer (celecoxib) at relieving joint pain and stiffness associated with osteoarthritis

• Safe; no systemic exposure, no contraindications, no known interactions with medicines
• Revolutionary approach using physical biolubrication to target osteoarthritis directly, rather than mask the pain
• Drug-free, so can be used in conjunction with medications and for long-term treatment
• Wider choice of marketing opportunities than its competitors as it is classed as a medical device

Current prescription products (including topical NSAIDs) in the United States carry black box warnings highlighting the class risks associated with their use. Medical advice is typically to use the lowest dose for the shortest possible time, on the fewest possible joints. FLEXISEQ does not have these limitations, so is a more attractive option for long-term pain relief.

Forward Looking Statements

This press release, business update and change of name contain forward-looking statements. All statements contained in this press release, business update and change of name that do not relate to matters of historical fact should be considered forward-looking statements, including, but not limited to, statements regarding the Phase II clinical trial of SelectAte, assessments of the commercial position of the Company’s products both in market and in development and the Company’s development strategy.

These forward-looking statements are based on management's current expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from our expectations expressed or implied by the forward-looking statements, including, but not limited to, the following: our limited operating history; our need for additional funding to complete development and commercialisation of SelectAte and our other haemophilia products, which may not be available and which may force us to delay, reduce or eliminate our development or commercialisation efforts; the reliance of our business on the success of some or all of its products; economic, political, regulatory and other risks involved with international operations; the lengthy and expensive process of clinical drug development, which has an uncertain outcome; serious adverse, undesirable or unacceptable side effects associated with SelectAte and our other haemophilia products, which could adversely affect our ability to develop or commercialise SelectAte and our other haemophilia products; potential delays in enrolling patients, which could adversely affect our research and development efforts; we may not be successful in developing SelectAte or our other haemophilia products; our ability to obtain approval for and commercialise SelectAte and our other haemophilia products in multiple major pharmaceutical markets; misconduct or other improper activities by our employees, consultants, principal investigators, and third-party service providers; the loss of any key personnel and our ability to recruit replacement personnel, material differences between our “top-line” data and final data; our reliance on third parties, including clinical investigators, manufacturers, distributors and suppliers, and the risks related to these parties’ ability to successfully develop and commercialise SelectAte and our other products; and lawsuits related to patents covering SelectAte and our other products and the potential for our patents to be found invalid or unenforceable.

These and other important factors set out in our publicly filed Annual Report and Accounts from time to time, could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release, business update and change of name. Any such forward-looking statements represent management's estimates as of the date of this press release, business update and change of name. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release, business update and change of name.