Nuformix plc (LON:NFX), a pharmaceutical development company targeting unmet medical needs in fibrosis and oncology via drug repurposing, has announced its audited results for the eighteen months ended 30 September 2023 following the change in the Company’s accounting reference date from 31 March to 30 September.
Non-Executive Directors’ Statement
Introduction
The key priority for the directors continues to be to focus on the Company’s early-stage pipeline of preclinical assets and ensure strength in the areas of drug development, business development and financial control within the Group. We operate a lean structure with the limited Board and bring in specialists and consultants, experts in their field, to support the business as required.
Pipeline
Nuformix has an early-stage pipeline of preclinical assets in development to address the high unmet medical need in fibrosis and oncology. We target solutions using our expertise to develop and file patent applications on novel crystalline forms of existing, marketed drugs, that have improved physical properties, with the aim of developing novel products in new indications to create attractive commercial opportunities. Importantly, the commercial opportunity is optimised when the repurposed product is differentiated from the original marketed drug by way of either dose, route of administration or presentation.
Drug repurposing is a well-known and successful strategy for enhancing the therapeutic and commercial value of marketed drugs, and their development typically brings a greater probability of success compared to developing newly discovered drugs, due to the existing data that has been generated on the marketed drug. This existence of data may also result in lower overall development costs and shorter development timelines.
The Group’s business model is to take these assets to key value inflection points before partnering or licensing. We conduct our R&D activities through out-sourcing, to enable us to access the different types of expertise that are needed for drug R&D and to minimise our operational costs. We have a strong network of external contractors, with whom we have had relationships over many years.
NXP002 (novel proprietary form of tranilast) – Idiopathic Pulmonary Fibrosis (“IPF”)
NXP002 is the Group’s preclinical 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, which allows the drug 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 (now off patent) achieved US$3.5bn and US$0.8bn respectively in 2022.
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 use 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 their debilitating systemic side-effects.
Effective inhalation therapies offer the potential to overcome these limitations of oral therapies. Nuformix owns granted patents protecting new forms of tranilast, in addition to a recently filed patent protecting its use with SoC in IPF, with patent prosecution progressing in major pharmaceutical territories.
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 Standards of Care (SoCs) 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 preclinical 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.
Nuformix plc 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 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 inflammatio
· 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 preclinical 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 (“TPP”) that is consistent with twice daily inhalation administration. To assess NXP002’s duration of action in relation to the TTP, the Company initiated work in an exploratory model in healthy human lung tissue. The model also bridges the Company’s successful preclinical 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 TTP 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.
Post-period end on 23 October 2023, the Company announced that it was issued with an Official Decision to Grant Notice of Allowance for Japanese National Phase Patent Application No. 2020-555115 entitled “CRYSTALLINE TRANILAST SALTS AND THEIR PHARMACEUTICAL USE”. This patent, which has already been granted in the US, describes proprietary new forms of the drug tranilast being progressed by the Company as a potential novel IPF treatment. These proprietary drug forms uniquely enable delivery via an inhaled nebulised formulation.
NXP004 (novel forms of olaparib) – Oncology
The Group discovered novel forms of olaparib, a drug currently marketed by AstraZeneca, as 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$2.6bn in 2022 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 preclinical 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 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) exclusively licensed to Oxilio for oncology indications.
On 18 September 2023, the Company announced that Oxilio had acquired ownership of its NXP001 patent estate for which Nuformix received new immediate and near-term undisclosed milestone payments, whilst retaining further development milestones and royalties capped at £2 million per year.
Fundraising
On 13 April 2023, Nuformix plc completed a subscription to raise gross proceeds of £70,000 through a subscription for 35,000,000 new ordinary shares of 0.1 pence each in the capital of the Company at a price of 0.20 pence per share. The Subscription was undertaken with a single UK-based FCA regulated institutional investor. The New Ordinary Shares represented 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 are exercisable for two years from 21 April 2023. 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 the 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 are being used by the Company primarily to further advance its NXP002 programme for the inhaled treatment of IPF.
Lanstead Subscription and Sharing Agreements
During the period the Company received proceeds from the Company’s subscription and associated sharing arrangements with Lanstead Capital Investors L.P., as announced on 14 December 2021, 17 January 2022 and 12 April 2022. The sharing agreements ended in October 2023, concluding this arrangement and the Company is due no further funds from Lanstead.
Business Development
During the period the Company has switched its focus to business development activities to explore partnering opportunities for both its NXP002 and NXP004 programmes, attending both the European Respiratory Conference in Milan and the IPF Summit in Boston. Those partnering activities are ongoing.
Summary and Outlook
The strategy of Nuformix plc is to continue to optimise value from its existing assets while maintaining tight control of costs. The proceeds from the Lanstead Sharing Agreements, the April 2023 fundraise proceeds and the milestone payment received from Oxilio in September 2023 and post-period in December 2023 have enabled the Group to continue to advance and exploit the current assets within the portfolio through selective additional R&D and business development activities as set out above. The Group is conducting business development/licensing activities for all its assets using a structured and data-driven approach, with the goal of seeking global licensing deals. Our focus and emphasis is to progress our NXP002 and NXP004 programmes where required to complete licensing transactions and achieve value creation to generate a return for shareholders.
We would like to thank all stakeholders and in particular our shareholders for their continued support and we look forward to the remainder of the year and beyond with confidence that significant value can be realised from our portfolio of assets over time.
