Roundtable Discussion; The Future of Mineral Sands. Watch the video here.
Soup is this an old study?
Value:
£43,814
Funded Period:
Jun 15 - Mar 16
Funder:
Innovate
Abstract
Funding
details The project will evaluate the feasibility of inhaled delivery of a cocrystal-enabled known drug
to treat idiopathic pulmonary fibrosis (IPF) in-vivo.
The 1st therapies for IPF - a growing disease (5000 UK patients diagnosed/year*) with high
mortality (50% die in 2-3 years of diagnosis*) were approved in 2014 (Pirfenidone &
Nintedanib). These new therapies do not prevent disease progression and as oral treatments
have highly undesirable side-effects. The project aims to show that by delivering a more
effective drug directly to the lung, the efficacy of treatment can be increased without side
effects. There are 4 innovative aspects:
1. Inhalation for IPF is a novel concept & enables drug delivery direct to the site of need,
increasing efficacy and minimising undesirable drug exposure. >80% of patients have the
lung function to use a dry powder inhaler (DPI)**.
2. The active ingredient will be Tranilast – a Japanese oral asthma drug with a strong safety
profile. Tranilast is also well validated as an anti-fibrotic agent and therefore has new potential
for use in IPF.
3. Cocrystal technology can improve key physical properties for drug molecules. Tranilast is
highly insoluble and cocrystal technology will improve lung solubility & biodistribution,
maximising performance. This cocrystal application would be a 1st for inhalation.
4. Bleomycin is an accepted IPF disease model but has limitations. The Lung Slice Culture
(LSC) model addresses its problems & reduces the number of animals used, but is less
validated. The 2 models have not been compared using the same drug. This novel combined
approach will further validate both the result and the LSC model for future studies.
5. The processes & devices used for DPI delivery in-vivo are limited and less validated than
other methods. The study will develop reliable processes to investigate the delivery concept
that matches the envisaged end product (DPI).
*NHS data
**Prof. G. Jenkins
https://gtr.ukri.org/project/0492A76A-AB08-4B22-9F18-6888FD732F00#/tabOverview
From June
NXP004
NXP004 represents novel forms of an undisclosed marketed oncology drug that has significant sales (more than £1 billion per annum in 2020) and is showing further growth. Nuformix filed one patent application on novel forms of this drug in 2020. Further outsourced research, through an expert contract organisation, on additional new forms and their properties has now commenced. If the research is positive, further patent applications may be filed.
From today
NXP004 patent application filing
Nuformix plc (LSE: NFX), a pharmaceutical development company targeting unmet medical needs in fibrosis and oncology via drug repurposing, announces that it has filed a new patent application in relation to NXP004.
This filing covers a new family of co-crystalline forms of an undisclosed marketed drug that is approved globally for the treatment of several cancers and that had global sales of over £1bn in 2020. This is the second patent application related to NXP004 that Nuformix has filed and it complements the previous patent application on NXP004 co-crystals, thus expanding the Company's intellectual property portfolio.
Anne Brindley, Chief Executive Officer, Nuformix, commented: "We are pleased to have filed this new patent application for NXP004. Data that we have generated on these new co-crystal forms in the past six months has shown improvements over the marketed form that justifies filing this new application. This application, if granted, will strengthen the patent estate for NXP004 and Nuformix's IP portfolio as a whole."
Milwaukee - 11 November 2021: IQ-AI Limited (LSE: IQAI) (OTCQB: IQAIF), a developer of medical image processing platforms that have led to effective therapeutic strategies for brain tumor and other patients, and St. Jude Children's Hospital (Memphis, TN), have entered into a Data Use Agreement. The Agreement is a specific type of agreement required under the Health Insurance Portability and Accountability Act (HIPPA) Privacy Rule. It will provide Imaging Biometrics (IB) access to paediatric imaging datasets for use in the development of its patented, artificial intelligence (AI) technology, IB Zero G.
St. Jude Children's Hospital is the only National Cancer Institute (NCI)-designated Comprehensive Care Centre devoted solely to children. It has received the NCI's highest ranking of "exceptional" and has treated children from all 50 US states and from around the world.
Through this Agreement, IB will have access to a wide array of magnetic resonance (MR) datasets acquired in children of all ages. Diverse and accurately labelled (annotated) data are critical for developing and refining AI models. High quality data enables AI models to accurately analyze new, incoming, real-world image datasets. IB Zero G will use this data to generate synthetic contrast-enhanced images for paediatric neuro examinations.
Gadolinium Based Contrast Agents (GBCAs) have been used clinically in MRI examinations for decades and provide invaluable diagnostic information. In 2006, safety concerns were raised for GBCA use in patients due to the causative effect in a condition called nephrogenic systemic fibrosis (NSF). Since then, the awareness and understanding about GBCA use has escalated worldwide. More recently, it was found that repeated exposure of GBCAs result in its retention throughout the body. While the long-term adverse side effects are not known, the detrimental concerns for critical periods of life and especially on rapidly developing bone or brain, remain.
"This Agreement will accelerate the development and commercialization of IB Zero G," said Trevor Brown CEO of IQAI "Avoiding the use of GBCAs while preserving the diagnostic quality on paediatric images will help clinicians address concerns relating to GBCA retention and ultimately provide better care," he added.
Nuformix plc (LSE: NFX), a pharmaceutical development company targeting unmet medical needs in fibrosis and oncology via drug repurposing, announces that Dr Alastair Riddell, currently Non-Executive Chairman, will assume the role of Executive Chairman with effect from 1 December 2021.
Lol!!
Chill flick the bean soup. I was just pointing out it’s not a good look to pretend you have inside information then gloat about it on a public bulletin board. Surprised the fun police haven’t removed the post!
Lol!!!
He didn’t get any leak, A broken clock is always right twice a day he spent 8 months saying the same thing so was bound to get it right sooner rather than later!! Exactly what he’s doing now! We are all awaiting the same thing it will come just wait!!
The guys just bonkers!! We are all fully aware news is due on 2 fronts to keep pretending you have inside info just makes you look stupid!! IMO!!
It will come when it comes and with how tight the ship now is I can’t see any leaks!! Spoke to my broker this morning and he agrees no leaks just retails p+d !!
Patience it will come!! Hopefully lol!!
January, February, and March (Q1)
April, May, and June (Q2)
July, August, and September (Q3)
October 31st, November, and December 31st(Q4)
So I would say we’re roughly half way through Q4 so updates anytime now!! Would like to see separate updates for each product to give double boost to the current share price. Would also like them to address the ceo situation ASAP as to avoid unneeded uncertainty!!
Hopefully not asking for too much!!
GLA!!!
global deal package of around $360-450m, including upfront and milestones, plus mid to high single digit royalties on sales, based on recent market precedent, while there is potential for total deal value (upfront and milestones) to increase and royalties to rise to the mid-teens if a deal comes after NFX completes Phase I work on NXP002.
Beyond IPF, next steps in Fibrosis and Oncology
NFX has the option to investigate the scientific rationale for treating other diseases with NXP002 candidates for the broader fibrotic and oncology indications provided that the proof of concept is established This includes alleviating hyper-inflammation of the lungs in COVID-19 patients targeting the NLRP3 inflammasone, a key pathway in many inflammatory lung conditions such as Acute Respiratory Distress Syndrome (ARDS) and a
21
NUFORMIX PLC ( NFX.L)| 10 March 2021
Allenby Capital
well-documented mechanism of tranilast7. The preclinical plan, which hinges on the feasibility and activity of NXP002 as delivered by the inhaled route, will also form a foundation for future studies in other lung diseases. There will be no additional expenditure allocated to other indications at the preclinical stage by NFX as firstly NFX is focussed on IPF as the disease target and secondly, several of the evaluation steps, including the confirming feasibility of administration via nebuliser and inhalation safety, would be the same for any lung disease.
Many of the epidemiological risk factors and biological processes that lead to viral-induced ARDS are shared with IPF. In addition, many of the current and emerging antifibrotic drugs could have therapeutic potential for treating severe COVID-19 and certain experts believe the burden of fibrotic lung disease following SARS-CoV-2 infection is likely to be high8.
NFX has applied for a grant to advance the NXP002 programme via Innovate UK , and the outcome is due to be announced in Q1 2021. The company intends to seek further non- dilutive funding through further grant applications in the future.
There are other options to explore once a preclinical package on NXP002 is ready, in future, extending into new indications in which pulmonary inflammation or fibrosis are common factors offering significant commercial potential. NFX will be in a position to evaluate these options and business development opportunities once an effective data package is in place.
Other key areas to explore based on peer reviewed literature include:
– Oncology – Multiple in-vitro/in-vivo studies have shown the significant potential of tranilast in pancreatic, prostate and colorectal cancer.
– Fibrosis – NASH, kidney fibrosis, large markets with huge unmet need.
GLOBAL MARKET OPPORTUNITY FOR NXP002
We look at the available market opportunity for NXP002 either as a monotherapy or as a combination therapy and in view of the changing landscape. As we have said NFX looks to take the programme to the next inflection point before seeking global business development opportunities. We consider that completion of the anticipated data packages, costing in aggregate approx. £2m over the next 18-months can be a major inflection point in terms of readiness for licensing and with an attractive market opportunity worth $3bn and growing, we calculate that NXP002 could command combined peak sales of £1bn in major markets.
OFEV and Esbriet have an average annual wholesale acquisition cost of $135k/$123k in US and around $65k in Europe. The patent expiry of OFEV and Esbriet could change pricing dynamics and so we use conservative assumptions, around 50% of prices of the incumbents, accepting that in reality this will be determined by clinical efficacy and side effect profile. On one side there will likely be more comparators in the market, but orphan disease status and differentiated modes of administration and mechanisms can justify pricing in line with the branded incumbents. A monotherapy is likely to attract higher pricing than a combination therapy, another factor that is yet to be elucidated.
Assuming that there is an approx. 0.05% prevalence in each population and assuming annual incidence of new cases of around 1.5% in Europe and US, with 60% diagnosed and 33% of the patient pool eligible for treatment, this equates to approx. 32,000 patients in US. 35,600 in Europe and 13,000 in Japan. At 33% penetration and an annual price of £52k in US, £24.5k in Europe and £38.5k in Japan, respectively gives a combined peak sales of £1bn for all major geographies, broken down as follows:
– US peak sales 32,000 x 33% x £52k = £544m
– Europe peak sales 35,600 x 33% x £24.5k = £288m
– Japan peak sales 13,000 x 33% x £38.5k = £164m
In the ‘traditional’ biotech model, drug development is a 10-year minimum process. With abbreviated timelines, a repurposed new physical form could be on the market as early as 2029 in US and Europe and 2030 in Japan following a bridging study, with patent expiry in 2038 (not including potentially available patent term extensions). We consider that the route of development and the fact that underlying drug is already known means that there is a higher likelihood of approval than via the standard drug development model, balancing the fact that NXP002 is a preclinical programme, but with the existing body of tranilast safety and PK data that NFX can leverage.
Considering that NFX is looking to prepare a package suitable for a global license deals for NXP002 in the main markets, this would position it to negotiate upfront, milestones and royalties with a partner proportionate with the stage of development. If it strikes a deal or deals at the preclinical stage then the return is likely to be a globa
COMMERCIAL POTENTIAL IN A HUGE AREA OF UNMET NEED
As we have said, the IPF pharmacotherapy market is worth $3bn across the largest populations of US, Europe, UK and Japan, currently shared by only two approved oral therapies. These therapies, although somewhat effective do come with a range of side effects and a proportion of patients do stop therapy due to tolerability issues Although there are a number of other promising targets in the pipeline, none are in the same class as NXP002 and most utilise a different mode of administration (oral or IV) compared to the inhaled NXP002. These factors and the severe nature of the disease leave room for additional innovative and disease modifying therapies.
The evidence that up to 40% of patients are not being prescribed disease delaying treatment indicates that there is still much more work to be done to help patients, plus much more to learn about the disease and its multiple drivers. In the words of one Key Opinion Leader, despite the benefits of current treatments, we ‘still have a desperate need for drugs that make people feel better, that have fewer side effects, and that have a more profound impact on patient outcomes.’
There are around four other later stage inhaled/nebulised products in the pipeline, including reformulated Esbriet and OFEV being developed by Avalyn Pharma Inc. Judging by the rate of progress, one of the most advanced includes Fibrogen’s Anti-CTGF mAb, pamrevlumab, delivered as an IV injection. The recent late stage failure of former front runner ziritaxestat/ Galapagos/Gilead narrows down the field somewhat. Analysts peg a market launch in 2022 of pamrevlumab and peak sales of up to $1.5bn.
The IPF patient population comprises approx. 350,000 people in the key countries and is growing at a rate of around 1.7% per annum and the US alone accounts for around 60% of cases. The size of treatment market is forecast to increase at a CAGR of 8% this decade along with incidence of new cases and with the projected approval of additional therapies to reach more than $4bn by 2030. There are a number of late stage candidates looking at a variety of biological pathways including those indicating inflammatory or fibrotic risk or which have prognostic value. A cross-section of the most promising are shown above. Note that many have Fast Track Designation and/or Orphan Drug Designation factors that can accelerate the review process and extend the period of market/data exclusivity and so this is also an option for NXP002.
the combination of NXP002 with standard of care provided strong evidence of additional effects compared to standard of care alone on both fibrotic and inflammatory markers. In addition, the results showed evidence of similar or better activity of lower doses of standard of care in combination with NXP002, compared to higher doses of standard of care alone, indicating a potential for a dose-sparing effect of the combination.
Adding value via inhaled delivery
NFX has particular expertise in inhaled therapeutics: CEO Dr Anne Brindley brings broad experience including a deep range of contacts drawn from the prior development and commercialisation of inhaled products, including Symbicort® and flutiform®, which are core products in a global asthma and COPD therapy market worth over $30bn6 , including at inhaled products specialist Skyepharma (now Vectura) and at Glaxo, AstraZeneca and J&J. The particular benefits of inhaled therapies include:
– Delivery direct to the site of action for lung diseases, achieving drug levels in a high concentration in the target tissue to produce a therapeutic effect via a dose which is a fraction of the oral dose (inhalation doses are typically in micrograms vs oral doses of milligrams).
– Reductioninsystemicsideeffectsbyvirtueofthelowerdosesnormallyrequired to elicit a positive effect
– Avoidinglivermetabolismtomaximisetheamountofdrugavailableinthebody to exert positive effects
– Faster onset of action directly to the main site of disease. 6 Analyst estimate
17
– Successful precedent set in other lung diseases for example, asthma, COPD, Cystic Fibrosis, for a range of therapies (anti-inflammatories, bronchodilators, antibiotics)
– Potential for real therapeutic value-adding, not just extending the IP.
– Thepotentialtocomplementstandardofcareadministeredviaadifferentroute
e.g. oral medicines, as a combination treatment for lung disease like IPF.
NFX’s initial focus is on developing a formulation of the drug to facilitate inhalation by the patient and intends to test the feasibility of rapid and deep penetration of the drug into the lungs using a nebuliser in the first instance during the early stage studies. While tranilast is generally well tolerated, uncommon adverse effects include liver and kidney problems that can be alleviated by reducing the dose. Nebulisation is an appropriate delivery system for a disease such as IPF, where lung function can be limited and additionally it is a cost-effect method of delivery especially for early studies.
Promising early data
There are limited, but promising, early data on NXP002 in preclinical lung tissue models, reported in December 2018, supporting the rationale in treating IPF and other fibrotic lung conditions. NFX carried out multi-patient tissue studies in partnership with Newcastle Fibrosis Research Group (NFRG) at Newcastle University, a renowned expert group in fibrosis disease models using a leading-edge human tissue model that closely replicates the clinical disease:
– Data demonstrates NXP002 inhibits fibrotic markers ex-vivo, even in very severely fibrotic patient tissue, giving strong support for treating IPF and other fibrotic lung conditions.
– In addition, NXP002 demonstrated specific action measured against key inflammatory targets that are relevant in IPF.
– NXP002 out-performed current standard of care treatment, pirfenidone (Esbriet).
Further
NEW LIFE FOR A SUCCESSFUL CANCER SUPPORTIVE CARE DRUG
After NXP002, the next most advanced programme is NXP001 which shares the same API as Merck’s globally marketed cancer supportive care treatment.
NXP001 is a Phase I co-crystal form of the NK-1 antagonist, aprepitant, which is the active ingredient in EMEND (Merck) marketed globally for the treatment of Chemotherapy- induced nausea and vomiting (CINV). NFX has developed Phase I data on the candidate showing that it is bioequivalent to EMEND.
CINV is one of the most crippling toxicities associated with cancer treatment, and up to 30% of all people suffering from cancer are advised to undergo chemotherapy and around 70% to 80% patients suffer from CINV. Managing CINV can mean the difference between a patient choosing and staying on chemo, successfully completing the course of treatment or discontinuing it.
NFX has a number of other options for the programme over and above CINV which are currently being evaluated under its agreement signed in September 2020 with the private company, Oxilio, which has an option to licence NXP001 for the development in oncology, rather than in oncology supportive care.
Aprepitant has a number of known properties, notably the NK-1 receptor is involved in cellular responses such as pain transmission and modulation of cell proliferation. Also it acts as a neuromodulator contributing to brain function associated with depression, stress, anxiety, and nausea. Its success in CINV is based on controlling the vomiting reflex. This compound has also shown antiproliferative properties in tumoral cell lines of glioma, neuroblastoma, retinoblastoma, pancreas, larynx, colon, and gastric carcinoma9.
Existing data
In May 2019 NFX reported initial data from a pilot study of a proprietary co-crystal-based formulation developed within the NXP001 programme in healthy subjects, which demonstrated bioequivalence to Merck's EMEND at 125mg both in terms of peak exposure and overall exposure using the most well accepted measures, maximum concentration (Cmax) and Area Under the Curve (AUC). This was achieved without complex formulation, implying that there is room for adjustment in future.
There has been limited disclosure by NFX on the next steps and this is largely because Oxilio has the first option on NXP001 that will likely determine the next course of action and because NXP002 is the current priority. We assume that key points of differentiation might include overcoming problems with side effects include including tiredness, and GI impact. The co-crystal form may also overcome its insolubility and stability and offer a new mode of administration. For example, a liquid format rather than the capsule based EMEND could be valuable for severely ill, incapacitated people or to suit new treatment settings.
NXP004 – REPOSITIONING A BLOCKBUSTER
NXP004 is an oral co-crystal form of an undisclosed oncology drug. The underlying drug is a blockbuster oncology therapy, a small molecule drug with mechanisms that could also have utility in fibrosis.
NFX is engaged in developing a robust and defensible IP position on NXP004, through generating more research data, before disclosing the underlying drug and seeking to license the IP.
NFX’s strategy is to license the IP primarily for its existing oncology indications, as, in this case, the NFX IP on NXP004 could be of interest to the originator of the marketed drug as a means to extending its own patent estate to protect this high value drug in oncology.
Thus, NFX has the option to pass the technology and the new form back to the originator in order to extend the patent life of this high value drug in oncology. There is one patent application filed, and a second in progress – if granted, with potential expiry around 2041. Other licensing options include seeking a deal with a generic drug developer.
However in addition, we do know that there is already early but encouraging data from a preclinical pilot study on NXP004, reported in August 2020, in fibrosis.
The study evaluated NXP004 in human tissue in IPF compared to standard of care and focusing on the over-proliferation of extracellular matrix (ECM) components as a driver of IPF progression, differentiated from the main anti-fibrotic and anti-inflammatory mechanisms of NXP002/tranilast.
– NXP004 showed a dose-dependent reduction in the secretion of several key ECM components.
– These data suggest NXP004 compares favourably to current standard of care with regard to anti-fibrotic activity in this model.
The pilot study was interrupted as research partner Newcastle Fibrosis Research Group’s (NFRG) facilities were commandeered on Government orders to support COVID testing.
While there is literature evidence for this drug’s activity in fibrosis, the Company’s strategy to derive most value for this asset is to pursue opportunities in oncology as a priority.
Why don’t you just look rather than ask it’s a click of a button rather that type out a question just seems you’re asking a question you already know the answer to hence the replies you received!
Trades 99
Vol. Sold 4,505,875
Sold Value £80.88k
Vol. Bought 4,139,511
Bought Value £74.30k