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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
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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
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– 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
Preclinical studies show potential for single agent and combination use. Data from an in vitro IPF model has shown anti-fibrotic/anti-inflammatory activity of NXP002 alone and in combination with two approved IPF drugs. These studies suggest the addition of NXP002 may achieve the same or better activity at lower doses of the approved drugs, which may offer advantages as both have challenging side effects. Additional preclinical studies are planned as Nuformix builds out a more robust data package. Results due Q4 2021
Progress on NXP004. Research is also underway on developing new forms of an undisclosed marketed oncology drug (with sales c.$1.5bn in 2020). Results Due Q4 2021.
A patent filed in 2020 may be granted in 2022.
Licensing deal under negotiation with Oxilio. A licensing deal has been finalised with Oxilio, a private UK company, for NXP001, a novel formulation of aprepitant intended for cancer treatment.
Under the terms of the licensing agreement, Oxilio has obtained an exclusive licence to research, develop and commercialise NXP001 globally for oncology indications. Nuformix is eligible to receive an undisclosed upfront payment, development milestone payments and a royalty on net sales, capped at £2 million per annum.
Indicative value NXP002
. We believe a licensing deal or partnership for NXP002 as a Phase 1-ready asset for IPF could have a $360-450m headline value, although the upfront would be likely to be in the $10-20m range. Although, the economics of such deals are difficult to predict, the future NPV of this asset alone could be +£50m.
Fully funded
Cash to 2023. Nuformix results show net cash of £1.6m, giving a runway into late CY2022
Re-cap for newbies06
Preclinical studies show potential for single agent and combination use. Data from an in vitro IPF model has shown anti-fibrotic/anti-inflammatory activity of NXP002 alone and in combination with two approved IPF drugs. These studies suggest the addition of NXP002 may achieve the same or better activity at lower doses of the approved drugs, which may offer advantages as both have challenging side effects. Additional preclinical studies are planned as Nuformix builds out a more robust data package. Results due Q4 2021
Progress on NXP004. Research is also underway on developing new forms of an undisclosed marketed oncology drug (with sales c.$1.5bn in 2020). Results Due Q4 2021.
A patent filed in 2020 may be granted in 2022.
Licensing deal under negotiation with Oxilio. A licensing deal has been finalised with Oxilio, a private UK company, for NXP001, a novel formulation of aprepitant intended for cancer treatment.
Under the terms of the licensing agreement, Oxilio has obtained an exclusive licence to research, develop and commercialise NXP001 globally for oncology indications. Nuformix is eligible to receive an undisclosed upfront payment, development milestone payments and a royalty on net sales, capped at £2 million per annum.
Indicative value NXP002
. We believe a licensing deal or partnership for NXP002 as a Phase 1-ready asset for IPF could have a $360-450m headline value, although the upfront would be likely to be in the $10-20m range. Although, the economics of such deals are difficult to predict, the future NPV of this asset alone could be +£50m.
Fully funded
Cash to 2023. Nuformix results show net cash of £1.6m, giving a runway into late CY2022
Worth rewatching recent interview with CEO she states everything going very well both NXP002 and NXP004
https://www.youtube.com/watch?v=oqUq_8Jt8Ug
The price would probably be point 5 if I have sold my holding soup.
My negativity is aimed at the bod and their lack of respect they have for shareholders and not at the pipeline all Hope I have left here is in the product’s and the results of trials the bod have had no input in speak for themselves and then even our part time bod might manage to salvage a deal, provided they outsource a good business development manager!!
Just frustrated and can see that with the ceo soon to depart the uncertainty will be hanging over us for a while yet!!!
Everything is as it pleases them!! Couldn’t give a flying feek about shareholders!
You must be delusional if you think a deal will be sealed before Anne runs off into the sunset!!
“Anne rides with head held high” lol!!
She’s being given 10k per month other than 3/4 interviews I recall ? With the first couple reading off a script?What else has she done?
Certainly nothing that has been reflected in the share price.
So no value added at all!! More value destruction if anything
Good luck all imo we’ll need it!!
“You’re really want to get rid of a seriously good CEO who has previously developed massive drugs and an inhalation simulation for GSK because you think you know their day to day routine better than them?”
It’s going to happen sooner than later so they may as well get it over with! It’s going to knock another 10/15 percent off the share price when announced so yeah I’d prefer they just got it over with!!
Have I touched a nerve there in regards to nxp001? That’s exactly what’s happened open your eyes!! It was you that made everyone aware!!
Anne has done nothing but put us at least a year behind imo I’ll be happy to be proved wrong
“if you think that Brindley (who has previously developed a blockbuster $bn+ inhaler based drug) is sat around doing nothing then you clearly haven't a clue on what NFX is actually about.”
Sorry soup but for a company that has outsourced EVERYTHING (apparently public relations also) I do wonder exactly what if anything she does on a daily basis ? The market doesn’t think so
Come on you’ve been around long enough to see we’re all being taken for a ride. Even our old ceo has practically taken one of the products for peanuts? Why not disclose details why no broker update just ignore it and it will go away!!
It’s a joke and the problem is the uncertainty around the ceo. Feek the data it can wait they need to stabilise the ship then resume. Nfx are a laughing stock at the moment and until this issue is resolved it will stay that way.
I have a lot of respect for you for the time you put in here and how you help people more than the company does. But really it shouldn’t be a guessing game should it!
I have emailed the company and will share the response if I receive one that is.
Good luck all!!
And normally pi’s are the last to know anything so the way this has dropped off a cliff and they have removed a document which stated everything is going well from their website tells me they already know we’re feeked!
All in my opinion