Nuformix plc (LON:NFX), a pharmaceutical development company targeting unmet medical needs in fibrosis and oncology via drug repurposing, has announced its unaudited results for the twelve months ended 31 March 2023 following the change in the Company’s accounting reference date from 31 March to 30 September.
Operational highlights
· The Company successfully conducted studies in state-of-the-art 3D human Idiopathic Pulmonary Fibrosis lung tissue, using a disease and species relevant model, which initially focused on the anti-fibrotic action of NXP002 in combination with current standards-of-care (“SoC”). The results indicated:
o NXP002 alone delivered a strong, consistent anti-fibrotic effect as demonstrated by modulation of the release of multiple biomarkers of fibrosis; and
o Both high and low concentrations of NXP002 showed an additive anti-fibrotic effect to SoC.
· The anti-inflammatory action of NXP002 was subsequently investigated, post period end, in the same model and the results indicated:
o NXP002 alone delivered a strong, consistent anti-inflammatory effect as demonstrated by modulation of the release of multiple biomarkers of inflammation; and
o NXP002 increased the performance of SoCs in modulating the release of a panel of inflammation biomarkers associated with the progression of fibrotic lung disease.
· The Company additionally successfully conducted duration of action studies using an exploratory 3D human lung tissue model offering species relevance and NXP002 dosage control. This allowed investigation of NXP002’s anti-inflammatory action at various timepoints following challenge with lipopolysaccharide (“LPS”), a stimulant that induces measurable endpoints and pathways relevant to IPF progression. The results indicated:
o NXP002 suppresses the release of inflammatory cytokines by healthy human lung tissue following LPS challenge; and
o A strong anti-inflammatory effect remains at 12 hours post drug dosing demonstrated by continued suppression of the release of inflammatory cytokines following LPS challenge, confirming NXP002 has a suitable duration of action to support its Target Product Profile of twice daily dosing.
· In vitro dissolution comparisons of NXP004 co-crystals to Lynparza® (commercially available olaparib) demonstrated that the two lead NXP004 cocrystals selected out-perform Lynparza®, in terms of rate and extent of dissolution and release of olaparib.
Financial Highlights for the twelve months ended 31 March 2023
· Loss before tax £761,299 (31 March 2022: loss of £1,270,273).
· Loss on ordinary activities (after tax credit) of £760,136 (31 March 2022: loss of £1,108,994).
· Loss per share 0.11p (31 March 2022: loss per share 0.19p).
· Net assets of £4,228,204 (31 March 2022: £4,737,961) including £259,259 of cash and cash equivalents at 31 March 2023 (31 March 2022: £464,095).
· The Company’s accounting reference date and financial year end was changed from 31 March to 30 September.
· Post period end, on 13 April 2023, a subscription for 35,000,000 new ordinary shares at a price of 0.20 pence per share raised gross proceeds of £70,000. The subscription was undertaken with a single UK-based FCA regulated institutional investor. In addition, the participant in the subscription was issued with one warrant for every one new ordinary share subscribed for with an exercise price of 0.25 pence per warrant. These warrants could result in the issue of an additional 35,000,000 new ordinary shares raising a further £87,500 for progression of the Company’s business activities.
Dr Dan Gooding, Executive Director of Nuformix, said: “Our interim report demonstrates the Company is continuing to generate value-adding data for its lead programmes whilst further optimising its operational costs. For NXP002, our pre-clinical strategy has delivered consistently positive results that allow us to tell a complete pre-clinical story to potential licensing partners for the first time and demonstrate that inhaled treatment of IPF via NXP002 is a viable concept. Our near-term goals focus on our NXP002 programme, as we continue to generate robust data to support our out-licensing objectives, all achievable using existing funds thanks to our lean operational model which will continue to operate. We are greatly encouraged by our recent work in close-to-patient human tissue models, in particular the new data supporting NXP002’s duration of action and Target Product Profile. I am excited by our prospects for the remainder of the year as we formally commence partnering activities and look forward to sharing results as they emerge.”
Chairman’s statement
Following the change of the Company’s accounting reference date from 31 March to 30 September these interim results cover the 12 month period to 31 March 2023. The Company’s interim results for the six month period ended 30 September 2022 were announced on 13 December 2022 and the operational review below covers the subsequent period from 30 September 2022 to 31 March 2023, a period of further progress for the Company’s assets NXP002 and NXP004.
Operational review
NXP002 (new form of tranilast) – Idiopathic Pulmonary Fibrosis (IPF)
NXP002 is the Group’s pre-clinical lead asset and a potential novel inhaled treatment for IPF and possibly other fibrosing interstitial lung diseases (“ILDs”). It is a proprietary, new form of the drug tranilast, to be delivered in an inhaled formulation.
IPF is a devastating lung disease associated with a higher mortality rate than many cancers. Thus, IPF represents a high unmet medical need such that the requirement for improved treatment options represents a significant commercial opportunity. IPF is classified as a rare disease and presents a global commercial market that is forecast to grow to US$8.8bn by 2027. Sales of standard-of-care therapies OFEV and Esbriet achieved US$2.5bn and US$1bn respectively in 2021.
Tranilast has a long history of safe use as an oral drug for asthma, keloids and hypertrophic scarring, but there is growing evidence that supports its potential in other fibrotic conditions, including IPF. NXP002 is differentiated as it is a patent protected new form of tranilast that has been enabled for formulation and delivery direct to the lungs by inhalation, a new route of administration for this drug. The inhalation route is a well-known strategy for treatment of lung diseases to yield greater efficacy and reduce systemic side-effects compared to oral treatment. Discontinuation rates for standard-of-care IPF therapies can be as high as 80% in certain patient groups due to systemic side-effects. Effective inhalation therapies offer the potential to overcome these limitations of oral therapies. Nuformix has two patent families protecting new forms of tranilast, both of which have already been granted in major pharmaceutical territories, with patent prosecution progressing in additional territories of interest. In addition, in March 2022, a method of use patent application was filed specific to IPF treatment.
As a potential treatment for IPF, which is a rare disease, NXP002 is a likely candidate for Orphan Drug Designation, which could provide additional product protection against potential competitors. The positioning of NXP002 as an inhaled treatment for IPF could be either as added to SoC’s or administered as a monotherapy for patients non-responsive to SoCs and those declining these therapies due to side effects which impact quality of life.
The pre-clinical inhalation strategy, initiated by the Company has significantly progressed NXP002 demonstrating:
· it can be delivered in-vivo by a range of nebulisers at the optimum particle size for delivery to the deep lung;
· very high doses appear to be well-tolerated; and
· an in-vivo inhalation dose response was observed for inflammatory and fibrotic biomarkers that is consistent with all ex-vivo human IPF tissue studies to date.
The Company conducted studies in a new iteration of a 3D human IPF lung tissue using a disease and species relevant model that has been advanced to significantly reduce output variability. The results from these studies of NXP002 alone and in combination with current standards of care (“SoC”), can be summarised as follows:
· NXP002 is well tolerated in ex-vivo human lung tissue with no signs of toxicity events;
· NXP002 alone delivers a strong, consistent anti-fibrotic and anti-inflammatory effect as demonstrated by modulation of the release of multiple biomarkers of fibrosis and inflammation;
· both high and low concentrations of NXP002 show an additive anti-fibrotic and anti-inflammatory effect to SoC;
· in particular, the higher concentrations of NXP002 with SoC’s deliver a near complete ablation of fibrosis biomarker release, yet at lower concentrations than have been seen in other pre-clinical models to date; and
· the clear, pronounced additive benefit of NXP002 on top of SoCs observed suggests that NXP002 will provide additional efficacy, even in patients responding to SoC therapy. This raises the possibility that NXP002 targets additional disease pathways to SoC’s when increasing the combined anti-fibrotic and anti-inflammatory response.
As announced on 18 May 2023, following success in suppressing biomarkers of fibrotic disease progression in human IPF lung tissue, the same samples were analysed to assess additional mechanistic and anti-inflammatory benefits on top of SoC’s and the results are summarised as follows:
· NXP002 alone delivers a strong, consistent anti-inflammatory effect as demonstrated by suppression of the release of inflammatory cytokines by over 90% for all cytokines studied; and
· the results further suggests that NXP002 will provide additional efficacy in combination with SoC’s, even in patients responding to SoC therapy alone.
Nuformix has developed a Target Product Profile that is consistent with twice daily inhalation administration. To assess NXP002’s duration of action in relation to the Target Product Profile, the Company initiated work in an exploratory model in healthy human lung tissue. The model also bridges the Company’s successful pre-clinical work across a variety of LPS-challenge studies. The results are summarised as follows:
· NXP002 suppresses the release of inflammatory cytokines by healthy human lung tissue following LPS challenge; and
· a strong anti-inflammatory effect remains at 12 hours post drug dosing demonstrated by continued suppression of the release of inflammatory cytokines following LPS challenge, confirming NXP002 has a suitable duration of action to support its Target Product Profile of twice daily dosing.
Overall, the results further strengthen NXP002’s potential for development as a new inhaled treatment for IPF either in addition to existing therapies or as a monotherapy. The Board continues to be encouraged by the progress of the studies and the positive data generated to date, in particular the recent duration of action study results and is focused on next steps which include:
· expansion of the current studies to include further human IPF tissue donors to demonstrate the robustness of NXP002’s anti-fibrotic response alone and in SoC combinations; and
· formally commencing the NXP002 partnering process.
NXP004 (novel forms of olaparib) – Oncology
The Group discovered novel forms of olaparib, a drug currently marketed by AstraZeneca, a Lynparza®. Lynparza® was first approved in December 2014 for the treatment of adults with advanced ovarian cancer and deleterious or suspected deleterious germline BRCA mutation. Since then, it has secured similar approvals in breast, pancreatic and prostate cancers with further trials on-going. These approvals have propelled Lynparza® sales to US$2.7bn in 2021 with industry analysts forecasting annual sales of US$9.7bn by 2028.
The Group has filed two patent applications on its novel forms of olaparib with the potential for patent life to 2040/2041.
The Company demonstrated enhanced performance of NXP004 cocrystals compared to olaparib. Subsequently, further preformulation studies allowed the Company to identify lead cocrystals to be progressed for further development.
Results from in vitro dissolution studies demonstrated that the two lead NXP004 cocrystals out-performed Lynparza®, both in terms of rate and extent of dissolution and release of olaparib.
Enhancement of dissolution in the currently marketed formulation of Lynparza® resulted in improved bioavailability versus the initial marketed product. Therefore, the NXP004 programme may offer potential to further increase olaparib bioavailability. In addition, the potential simplicity of NXP004-based formulations may offer improvements in product cost-of-goods versus the currently marketed product, which requires complex manufacturing methods.
These attributes position NXP004 for applications in line-extensions for the currently marketed product, or for possible development in future first-to-generic products.
The Company will now consider the design and execution of suitable pre-clinical pharmacokinetic models to further investigate and validate NXP004’s potential for enhancing the oral absorption of olaparib. Securing these data will enable commencement of discussions with multiple potential commercialisation partners.
This work will direct and support future out-licensing discussions for NXP004.
NXP001 (new form of aprepitant) – Oncology
NXP001 is a proprietary new form of the drug aprepitant that is currently marketed as a product in the oncology supportive care setting (chemotherapy induced nausea and vomiting). Nuformix granted an exclusive license to Oxilio Ltd (“Oxilio”), a privately held pharmaceutical development company, to license NXP001 globally for oncology indications on terms previously disclosed. A programme of formulation development was defined. Significant progress has been made exploring numerous formulation adaptations. This work is detailed, time consuming and ongoing. Despite Covid related supply chain issues Oxilio have generated more cocrystal supplies to allow this work to continue.
Fundraising
Post period end, on 13 April 2023, the Company completed a subscription to raise gross proceeds of £70,000 through a subscription for 35,000,000 new ordinary shares of 0.1 pence in the capital of the Company (the “New Ordinary Shares”) at a price of 0.20 pence per share (the “Subscription”). The Subscription was undertaken with a single UK-based FCA regulated institutional investor. The New Ordinary Shares represent approximately 4.7 per cent. of the Company’s enlarged issued share capital.
In addition, the participant in the Subscription was issued with one warrant for every one New Ordinary Share subscribed for with an exercise price of 0.25 pence per warrant. These warrants will be exercisable for two years from Admission (“Warrants”). If the Warrants are exercised in full, it would result in the issue of an additional 35,000,000 new ordinary shares raising a further £87,500 for progression of the Company’s business activities. The New Ordinary Shares and Warrants were issued pursuant to the Company’s existing share issuance authorities.
The net proceeds of the Subscription will be used by the Company primarily to further advance its NXP002 programme for the inhaled treatment of IPF.
Outlook
The Company to continues to advance and exploit the current assets within the portfolio through the R&D and business development activities as set out above. The sharing agreement with Lanstead provides cash on a monthly basis until October 2023 to the Company to fund its lean operations and together with the funds raised in the April 2023 Subscription will provide the Company with sufficient financial resources until any such time that the Group’s R&D and targeted partnering activities require further resource.
The strategy of the Group is to continue to increase the value of its existing assets while maintaining tight control of costs, including conducting business development/licensing activities using a structured and data-driven approach, with the goal of seeking global licensing deals.
Financial Review
In the period, the Board has continued to focus expenditure on R&D activities that add value to the current assets while optimising the operation to minimise administrative expenditure and the operational cost-base.
Dr Julian Gilbert
Non-Executive Chairman
22 May 2023
Statement of Directors’ Responsibilities
We confirm that to the best of our knowledge:
1. this interim condensed set of financial statements has been prepared in accordance with UK adopted IAS 34 ‘Interim Financial Reporting’;
2. the condensed set of financial statements has been prepared in accordance with ASB’s 2007 Statement Half-Yearly Reports;
3. the condensed set of financial statements give a true and fair view of the asset, liabilities, financial position and profit or loss of the group and the undertakings included in the consolidation as a whole as required by DTR 4.2.4R; and
4. the interim management report includes a fair review of the information required by:
4.1. DTR 4.2.7R of the Disclosure Guidance and Transparency Rules, being an indication of important events that have occurred during the first six months of the financial year and their impact on the condensed set of financial statements; and a description of the principal risks and uncertainties for the remaining six months of the year; and
4.2. DTR 4.2.8R of the Disclosure Guidance and Transparency Rules, being related party transactions that have taken place in the first six months of the current financial year and that have materially affected the financial position or performance of the entity during that period; and any changes in the related party transactions described in the last annual report that could do so.
The directors of Nuformix plc are listed in the Group’s 2022 Annual Report and Accounts and the current board are set out on the Investors Information section of Nuformix’s website at: Investors Information – Nuformix
Dr Julian Gilbert
Non-Executive Chairman
22 May 2023
Further copies of this document are available from the company’s registered address and will be available on the company’s website later today.
