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 six months ended 31 March 2024.
Operational highlights (including post-period end)
· The Board continues to be encouraged by the positive data generated to date on NXP002 in context to the evolving treatment landscape and understanding of future patient needs in the treatment of fibrosing interstitial lung diseases. Preliminary discussions have been initiated with potential partners and are on-going.
· Notice of Allowance was received for the Japanese National Phase Patent Application No. 2020-555115 for NXP002 entitled “CRYSTALLINE TRANILAST SALTS AND THEIR PHARMACEUTICAL USE” which has now formally granted. Notice of Allowance has also been received from the European Patent Office for the European National Phase Application, with formal granting complete. This patent describes proprietary new forms of tranilast being progressed by the Company as NXP002 as a potential novel idiopathic pulmonary fibrosis (“IPF”) treatment. These proprietary drug forms uniquely enable drug delivery via an inhaled nebulised formulation.
· Just prior to the beginning of the period, 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.
· During the period the Company received proceeds from the Company’s subscription and associated sharing arrangements with Lanstead Capital Investors L.P. (“Lanstead”). The sharing agreements ended in October 2023, concluding this arrangement and the Company is due no further funds from Lanstead.
· A subscription for 75,000,000 new ordinary shares at a price of 0.20 pence per share raised gross proceeds of £150,000, representing approximately 9.2 per cent. of the Company’s enlarged issued share capital.
Financial Highlights
· Loss before tax of £242,529 (31 March 2023: loss of £337,622)
· Loss on ordinary activities (after tax credit) of £242,529 (31 March 2023: loss of £337,622)
· Loss per share 0.03p (31 March 2023: 0.05p)
· Net assets of £4,102,051 (31 March 2023: £4,228,204) including £183,523 of cash and cash equivalents at 31 March 2024 (31 March 2023: £259,259)
Dr Dan Gooding, Executive Director of Nuformix, said: “Our research efforts and external discussions to date demonstrate that inhaled treatment of IPF and related fibrotic lung diseases via NXP002 is a viable and attractive concept. We remain focused on generating data and initiating, and further developing, discussions with potential partners that will support our efforts to secure out-license deals on NXP002 and NXP004. Progression of these opportunities is being achieved using existing funds thanks to a lean operational model, which will continue to operate until our R&D and targeted partnering activities require further resource. I am excited by our prospects for the remainder of the year and look forward to sharing results as they emerge.”
Chairman’s statement
Operational review
NXP002 (novel proprietary forms of tranilast): Interstitial Lung Diseases (“ILDs”) including Idiopathic Pulmonary Fibrosis (“IPF”) and Progressive Pulmonary Fibrosis (“PPF”)
NXP002 is the Group’s preclinical lead asset and a potential novel inhaled treatment for IPF and PPF and possibly other fibrosing ILDs. NXP002 is a proprietary, new form of the drug tranilast. NXP002’s enhanced physical property profile uniquely delivery to the lung in an inhaled, smart nebuliser formulation.
There are more than 200 types of interstitial lung diseases (“ILD”), which are characterised by varied amounts of inflammation, scarring, or both, that damage the lung’s ability to absorb oxygen. IPF is the most well-known form of ILD, affecting approximately 100,000 patients per year in the US. Progressive Pulmonary Fibrosis (PPF), previously referred to as Progressive Fibrosing ILD (PF-ILD), is a larger and even more poorly served segment of the ILD market, affecting more than 200k patients per year in the US.
IPF and PPF are devastating lung diseases associated with a higher mortality rate than many cancers with median survival of 3-5 years. Thus, IPF and PPF represent 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 (“SoC”) 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 while there is growing evidence that supports its potential use in other fibrotic conditions, including IPF, a combination of poor physicochemical properties, variable pharmacokinetics and challenging pharmacodynamics following oral delivery limit its potential use in ILDs. NXP002 is differentiated as it is a patent protected, novel form of tranilast that has been optimised for formulation and delivery direct to the lungs by inhalation, potentially overcoming the issues using tranilast orally as a chronic treatment for ILDs.
NXP002 as a potential treatment for IPF, is a likely candidate for Orphan Drug Designation, which could provide additional product protection against potential future competitors in addition to product development advantages.
The inhalation route is a well-known strategy for the treatment of lung diseases to yield greater efficacy and reduce systemic, off-target side-effects compared to oral treatment. Discontinuation of treatment in IPF and PPF patients is currently an issue in the treatment of these diseases with discontinuation rates for current SoCs up to 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.
The positioning of NXP002 as an inhaled treatment for IPF and PPF could be either as added to SoC treatments 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 Group’s pre-clinical inhalation development strategy has significantly progressed NXP002 towards validation of its Target Product Profile (“TPP”) demonstrating:
• NXP002 can be delivered in-vivo by a range of nebulisers at the optimum particle size for delivery to the deep lung;
• 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 ex-vivo human IPF tissue studies to date.
The Group 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 SoCs, 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 preclinical models to date; and
• the clear, pronounced additive benefit of NXP002 on top of SoCs observed suggests that NXP002 may 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. 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 suggest that NXP002 may provide additional efficacy in combination with SoC’s, even in patients not responding to SoC therapy alone.
Nuformix’s TPP for NXP002 seeks twice daily inhalation administration. To assess NXP002’s duration of action, the Group initiated work in an exploratory model in healthy human lung tissue. The model also bridges the Group’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
• an 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 duration of action that may support twice daily dosing.
Overall, the Board is encouraged by the progress of the studies and the positive data generated to date and is considering next steps, including potential further R&D studies to add further value to the programme and support on-going licensing activities.
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.
Subsequently, further preformulation and in-vitro studies allowed Nuformix 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, NXP004 may offer potential to further increase olaparib’s 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 product opportunities. 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) initially exclusively licensed to Oxilio Limited (“Oxilio”) for oncology indications. Oxilio has now acquired ownership of Nuformix’s NXP001 patent estate. Nuformix retained rights to receive further development milestones and royalties capped at £2 million per year under the terms of the acquisition.
Outlook
The Company continues to advance and exploit the current assets within the portfolio through the R&D and business development activities as set out above.
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 first half of the financial year, 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, Nuformix plc
18 June 2024
