Immupharma Share Discussion Threads

[butler4] 09/1/2018 09:33

Put your glasses on mate

[ny boy] 09/1/2018 09:33

Decent tree shake if we get 150p ish, clears the doubters and general unwashed out.

[wigwammer] 09/1/2018 09:31

"When the going gets tough.."Which chart are you looking at?!

[aussieb3] 09/1/2018 09:30

For some reason mm want to take this share lower after all yesterday buys this should be moving up not down. Giving people chance to buy some more before final push up

[herschel k] 09/1/2018 09:29

Volume is pitifulYou can read nothing into a drop like this

[butler4] 09/1/2018 09:27

Where have all the ‘fair weather’ commentators gone? When the going gets tough they all do a runner!

Nobody, not even Panamure, have any idea of the Imm potential until results are known - the call is each to our own

[kensingtoncourt] 09/1/2018 08:06

ytsa the historical data is the major positive as there was less than 2.5% probability the Phase 2b results were down to chance; but also the ongoing good safety in Phase 3, plus SPA, Fast Track status, poor competition in Benlysta, cheapness to manufacture, growing market, positive independently validated data in other indications, etc.

[money maker1] 09/1/2018 08:02

Did you see how HGSi's share price moved on their lupus drug. There are hundred of examples of share prices rerating on good news. How about a takeover.

[divmad] 09/1/2018 07:56

top tips,

Why do you expect the full value of $7bn for Lupuzor to be reached in Q1 2018, i.e. immediately after a successful read-out?

The actual share price trajectory here will not follow your idealised path, post-readout, that I'm sure of.

[ytsa2] 09/1/2018 07:54

Apart from historical results, what makes you so confident. Trials can be very unpredictable

[chadders] 09/1/2018 07:53

Article today summarising the bigger players investment in Alzheimer's

09/01/2018 12:57am
Dow Jones News


By Daniela Hernandez, Jeanne Whalen and Allison Prang
Efforts to find treatments for Alzheimer's disease suffered blows in recent days, but many companies, scientists and investors are still optimistic that they can find a way to treat the memory-robbing disease, which affects roughly 5.5 million Americans.

Axovant Sciences Ltd. on Monday shuttered development for a once-promising Alzheimer's drug, an announcement that came days after Pfizer Inc. said it was giving up on the space entirely.

"The mood is definitely negative on anything near-term, [but] there continues to be interest in this space," said Mark Ginestro, a principal for health-care and life sciences strategy at KPMG in San Francisco. "It's too big of a market to ignore. People are going to continue to go after it despite the roadblocks."

Roche Holding AG, Biogen Inc., Eli Lilly & Co. and others are still developing therapies. Startups with neuroscience pipelines, like Denali Therapeutics Inc. and Verge Genomics, are attracting funding, and so are early-stage research projects.

During the fiscal year 2017, the National Institutes of Health will have poured an estimated $1.35 billion into Alzheimer's disease, almost triple its investment for fiscal year 2013. And Pfizer said it had plans to establish a corporate venture fund focused on neuroscience projects.

Sales of successful treatments for the disorder could amount to billions of dollars as demand for therapies increase due to an aging population. Analysts had predicted that annual sales for Axovant's drug, known as intepirdine, could have topped $2 billion.

"It's too early to give up," said Paul Aisen, the director of the University of Southern California's Alzheimer's Therapeutic Research Institute in San Diego. "We're actually on the precipice of major advances. I would not discount all the disappointments over the years, but I believe we're in good shape."

The recent failures that have plagued the pharmaceutical industry and brewed much frustration among investors have been the result of a suboptimal approach to drug development, Dr. Aisen said. For years, the industry has focused on dementia, which happens at the latest stages of the disease, when reversing the damage done to the brain is difficult, if not impossible, he said.

Many of the drugs that have failed in large clinical trials have targeted beta amyloid, the sticky plaque in the brains of Alzheimer's patients that many scientists believe is a leading cause of the disease. But attacking these plaques in the brain didn't affect cognition.

Companies and researchers pursuing treatments are still pursuing amyloid in many cases, but they are beginning to focus on treating patients earlier in the disease process, before they show memory deficits or cognitive decline. New neuroimaging technologies, genetics and more sensitive cognitive tests are also helping clinicians to better understand how the disease progresses, and to potentially identify patients who could benefit from treatment before cognitive symptoms appear.

In some cases, patients are identified based on genetic testing that suggests they might be at a higher risk of developing the disease. Others have amyloid plaques, but don't yet have cognitive deficits.

Lilly's amyloid-targeted drug, solanezumab, failed to benefit patients in several large and costly studies in patients with mild to moderate disease. After the failure of one study in late 2016, Lilly said it had spent nearly $1 billion on the experimental drug, and about $3 billion total on Alzheimer's research over the past three decades.

But Lilly continues to test solanezumab in other human studies, including one funded by the U.S. government testing the drug in at-risk patients who don't yet have outward signs of the disease.

Merck & Co. last year stopped a clinical trial of an experimental Alzheimer's drug, verubecestat, because it wasn't helping patients with mild to moderate forms of the disease. The drug, a BACE inhibitor, aimed to prevent an enzyme from producing the sticky amyloid.

Merck said it would continue a separate study of verubecestat in patients at an earlier stage of Alzheimer's known as prodromal. Results from that study are expected in 2019.

"The question is, how early is early enough?" Roger Perlmutter, Merck's head of research and development, said in an interview. "None of this is easy...we recognize this is one of the hardest drug-development areas," he said, adding, "we simply do not believe it is acceptable to stand on the sidelines."

Biogen is currently testing another antibody that goes after amyloid possibly by stimulating microglia, the brain's scavenger cells, to chew up the plaques. In a recent study, higher doses of the drug, known as aducanumab, cleared more plaques, but adverse effects were more common. The drug slowed cognitive decline in patients with early Alzheimer's. Some scientists say that the drug could cause inflammation in the long-term, which would be detrimental to brain health. Results for larger trials are expected in 2020.

Merck and other companies have also focused attacks on a different protein, tau, that forms twisted proteins in the brains of Alzheimer's patients.

That approach suffered disappointment in 2016, when a closely watched trial of a tau-targeted drug developed by TauRx Pharmaceuticals Ltd. failed to improve patients' cognition or daily functioning in a clinical trial.

Even if companies can figure out how to reach patients earlier in the process, success may not be as simple as targeting one protein or another, scientists say. Some believe an interaction between beta amyloid and tau plays a central role in the disease. Others think there are many possible triggers, including some beyond beta amyloid or tau.

Combination therapies targeting several Alzheimer's-related proteins, like amyloid and tau, could be more fruitful. Biogen and Lilly said such multifaceted treatments are likely the future of Alzheimer's therapeutics.

Axovant's drug, intepirdine, inhibited signaling pathways in the brain. Scientists thought that it could help with cognitive decline. Other attempts at developing similar drugs have also failed.

Some companies are looking for treatments in the cutting-edge field of gene therapy, which introduces beneficial genes to the body to help fight disease.

Johnson & Johnson last week announced a collaboration with the University of Pennsylvania aimed at inserting certain genes into harmless viruses that would carry the genes to the cells. The genes would then instruct the cells to secrete beneficial antibodies that would fight Alzheimer's.

Once injected into the body, the viruses ideally would be able to cross the blood-brain barrier, which separates brain tissue from the rest of the body, Eric Schaeffer, senior director of neuroscience innovation at Johnson & Johnson, said in an interview. The research is at an early stage and could be four or five years away from human studies, he said.

Denali Therapeutics, a San Francisco-based biotech company that has multiple Alzheimer's treatments in its pipeline, went public last month. The company has three Alzheimer's drugs in preclinical development targeting tau and other mechanisms, according to its website. Denali also announced last week it is working with Japan's Takeda Pharmaceutical Co. to focus on neurodegenerative diseases like Alzheimer's.

Given the huge unmet need in Alzheimer's, there are incentives to try to make headway in the market, according to Ritu Baral, senior biotech analyst for Cowen. Big pharmaceutical companies tend to be more conservative, she said.

"Small to midcap biotechs are inherently [willing to be] riskier," she said. "Everything is an investment for the future."

--Peter Loftus contributed to this article.

Write to Daniela Hernandez at [e-mail], Jeanne Whalen at [e-mail] and Allison Prang at [e-mail]

[flavio_monteiro] 09/1/2018 07:49

Kensingtoncourt...I am confident its going to work on Lupus....and work really well. The other indicators are the Cream!

[kensingtoncourt] 09/1/2018 07:43

ytsa2 if Lupuzor failed in lupus (which I think is very unlikely based on the safety and efficacy to date) then it could still be used in combination with another lupus drug, and IMM or a partner just continue working their way down that growing list of indications (currently 12+) until they find ones in which it works best, and in relation to which SM said in her presentation they could go directly into Phases 2b or 3 because of their already substantial data so far. An analyst also said they understood Lupuzor resolved all of the arthritis measures, and that market is eight times bigger than for lupus. Like hottingup always says, Lupuzor or P140 will get to market for something, its just a question of how many indications - could be all 12 and the list is still growing.

[flavio_monteiro] 09/1/2018 06:47

In the DAILY MAIL today...

Pfizer abandons hunt for new drugs to treating Alzheimer's and Parkinson's disease after series of failures....

From the Immupharma web site.... Our amazing P140 Platform MAY come to the rescue.

Autophagy represents a key pathway that is targeted by the P140/Lupuzor™ peptide. Defects in this complex process underlie many types of diseases, including autoimmune, many inflammatory diseases, and degenerative neurological illnesses (e.g. Parkinson’s and Alzheimer’s diseases), and aging. Thus, therapeutic agents such as P140/Lupuzor™, are unique molecules that may significantly slow down or correct the course of such diseases and considerably improve the quality of the life of patients.

[ytsa2] 08/1/2018 22:03

You can work out as many possible revenue streams and values, but totally depends on PIII results. If positive will fly, if not flop

[top tips] 08/1/2018 21:39

Not that helpful but thanks anyway.

You yourself recently pointed out Gilean took over Kite in 2017 for $11 billion to get their platform, which was more important than revenues - and we know IMM has two platforms, including P140 (of which Lupuzor is part) which could be very high value.

However, on revenues, peak annual sales for IMM's Lupuzor, just in lupus, are likely to excede anything predicted for Benlysta (e.g. the $1 billion pa 2020 figure) and there are 12+ high value indications that could all generate revenues.

The best starting point of reference for read across to IMM is the GSK deal with HGSi for their Lupuzor drug Benlysta, with various add-ons to take account of other factors. Analyst Vadim Alexandre confirmed this in his presentation last July:

"HGSi's takeout price was $3.6 billion for 50% of the rights (to Benlysta) so we can assume roughly Benlysta was bought for $7 billion...and that's in 2012...so if we are looking at a drug (Lupuzor) that could be better, the price could be higher...a novel treatment for lupus could command that price...because it already has..."

Hottingup set it out quite well, moving forward from this:

hottingup
8 Jan '18 - 15:55 - 9045 of 9048
0 11 3
On the basis we assume Lupuzor produces good Phase 3 results in Q1 2018 then any valuation of Lupuzor must start as a minimum with the $3.6 billion paid in 2012 by GSK to acquire HGSi's 50% stake in lupus drug Benlysta - effectively valuing 100% of Benlysta at $7 billion.

To that $7 billion should then be added something for the following:

1) Inflation during what in 2018 will then be the last 6 years since 2012.

2) Lupuzor (I assume) being more efficaceous, having less or no side effects, being faster acting and cheaper to produce, than Benlysta.

3) Use in multiple blockbuster indications (including off label and on label) some of which have market sizes many times larger than for SLE lupus, e.g.

Lupuzor™ Symposium
8th June 2016 - 3:35 pm

41 min 40 sec onwards:


Indications with independently validated preclinical data:
- Systemic Lupus Erythematosus (SLE) (Market size $4 bn) (SLE ends Phase 3, Q1 2018)
- Neuropsychiatric lupus (NPSLE)
- Gougerot-Sjögren syndrome (GSS) (Market size $2.2 bn by 2024)
- Rheumatoid Arthritis (Market size $28.5 bn by 2025)
- Gougerot-Sjögren syndrome (GSS) (Market size $2.2 bn by 2024)
- Crohn's Disease + Ulcerative Colitis (Market size $4 bn by 2022)
- Guillan-Barre disease
- Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)
- Bullous Diseases (Market size $1.6 bn for Bullous Pemphigoid)
- Asthma (Market size $20.7 bn in 2015)

Other potential evaluations:
- Scleroderma (Systemic Sclerosis, Raynaud)
- Psoriasis
- Multiple Sclerosis (MS) (Market size $20 bn by 2024)
- (Others to follow)

Negative preclinical results for potential re-evaluation:
- Type I Diabetes (Market size $43 bn by 2021)
- Amytrophic Lateral Sclerosis (ALS)

(An analyst note states they, "understand that a majority of Phase IIb patients showed resolution of the arthritis measure (four point score...)".

4) New patent granted in key countries (USA, EU, China, India and Japan) covering Lupuzor up to 2032 and its use in the treatment of a majority of autoimmune diseases such as Sjogrens, rheumatoid arthritis, Crohn's and CIDP. (Announced 27/9/2017)

5) New patent has been filed (2017) to cover non-autoimmune indications. Further preclinical work continues at the CNRS with the objective of further indications moving into the clinic in due course. (Announced 27/9/2017)


Consequently the value of Lupuzor in Q1 2018 should be much greater than $7 billion (potentially multiples).

P.S.
In Mar 2009, HGSi shares (on 50% stake in Benlysta) were $0.45, becoming $3.23 (market cap $528m) early Jul 2009 just before PIII Benlysta results, $12.51 (market cap of $2 billion+) at close on results day late Jul 2009, and $34.49 ($6.46 billion market cap, as there was also some dilution) at peak in Apr 2010 = 76x return over 13 months from peak low to peak high.

[njb67] 08/1/2018 21:08

Some initial thoughts on the Celgene / Impact announcement and potential read across to IMM.

- Similar company profiles – one major asset in phase 3, no revenues
- Both have pipeline assets / further indications – will come to valuation of this in a bit
- Phase 3 is key for proof of commercial concept for both companies
- Similar size, both very small (10-20 employees)
- Both need a commercial partner to bring their medicines to market

Celgene have effectively placed a $1.1bn bet that Impact have managed to successfully circumnavigate the safety issues that led to Sanofi discontinuing clinical trials of fedratinib and that they can gain regulatory approval. If the Phase 3 results fail to overcome these concerns and secure a regulatory approval, this is how much Celgene will need to write off. Good to see that the market for small biotechs is alive and well.

If fedratinib is approved (not clear by whom – FDA, EMA, Japan, all etc.), then it will trigger a payment to the owners of $1.25bn ($150m for subsequent indications). Further payments, up to $4.5bn in total depend on fedratinib commercial sales.

Under the terms of the agreement, Celgene will make an upfront cash payment of approximately $1.1 billion. In addition, Impact Biomedicines’s shareholders are eligible to receive contingent payments based on regulatory approval and sales-based milestones. The maximum aggregate amount payable for regulatory approval milestones is $1.4 billion relating to approvals for myelofibrosis and other indications. Starting from global annual net sales of $1.0 billion, aggregate tiered sales-based milestone payments could total a maximum of $4.5 billion if global annual net sales exceed $5.0 billion (Impact Press Release 8 Jan)

Questions:
- Is the $4.5bn sales payment triggered if in any year fedratinib sales exceed $5bn, or is the amount that would be paid if annual sales exceed $5bn every year from now over the lifetime of the deal?
- How realistic is the $5bn target, very few medicines record this level of sales annually?
- If not realistic, them what additional payments could Impact secure on realistic sales forecasts (the additional payments only kick in once sales exceed a $1bn pa, blockbuster territory.
- How long does fedratinib have market exclusivity? Sanofi discontinued their study programme on safety concerns. How many years do they have left before generic competition sets in?

The (maximum) $7bn price paid is essentially a play on fedratinib. $1.25bn if they get FDA approval, $4.5bn if peak sales hit $5bn per year, with the remainder ($1.25bn) for the pipeline potential assets, securing regulatory approvals for these products, other patents, networks, infrastructure etc.


Implications for IMM
- The interest and market for promising compounds is strong. If we deliver on Phase 3, then we will have potential suitors. Someone may go early in the same way that Celgene have done. Check the RNS each morning.
- It is clear that companies place much greater value on the near term (Lup and Fedratinib) than pipeline assets, due to the cost of development and risk of failure. Over 80% of the value of the Celgene deal relates to Fed.
- Celgene are paying up to $7bn for peak (annualised?) sales of $5bn pa. With Benlysta sales currently at £300m pa and Lup targets around $1bn pa peak sales, this suggest a read across of around $1.4bn (£1.1bn) for IMM (Fed peak sales divided by 5). So roughly 4x current share price, or £8 per share.

Hope useful.

[jpleight] 08/1/2018 17:14

aussie my l2 screen has thebuys and sells

[slicethepie] 08/1/2018 16:44

Worth noting Panmure do not send their research to you now unless you are a paid client under new mifid 2 rules.

[hottingup] 08/1/2018 15:55

On the basis we assume Lupuzor produces good Phase 3 results in Q1 2018 then any valuation of Lupuzor must start as a minimum with the $3.6 billion paid in 2012 by GSK to acquire HGSi's 50% stake in lupus drug Benlysta - effectively valuing 100% of Benlysta at $7 billion.

To that $7 billion should then be added something for the following:

1) Inflation during what in 2018 will then be the last 6 years since 2012.

2) Lupuzor (I assume) being more efficaceous, having less or no side effects, being faster acting and cheaper to produce, than Benlysta.

3) Use in multiple blockbuster indications (including off label and on label) some of which have market sizes many times larger than for SLE lupus, e.g.

Lupuzor™ Symposium
8th June 2016 - 3:35 pm

41 min 40 sec onwards:


Indications with independently validated preclinical data:
- Systemic Lupus Erythematosus (SLE) (Market size $4 bn) (SLE ends Phase 3, Q1 2018)
- Neuropsychiatric lupus (NPSLE)
- Gougerot-Sjögren syndrome (GSS) (Market size $2.2 bn by 2024)
- Rheumatoid Arthritis (Market size $28.5 bn by 2025)
- Gougerot-Sjögren syndrome (GSS) (Market size $2.2 bn by 2024)
- Crohn's Disease + Ulcerative Colitis (Market size $4 bn by 2022)
- Guillan-Barre disease
- Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)
- Bullous Diseases (Market size $1.6 bn for Bullous Pemphigoid)
- Asthma (Market size $20.7 bn in 2015)

Other potential evaluations:
- Scleroderma (Systemic Sclerosis, Raynaud)
- Psoriasis
- Multiple Sclerosis (MS) (Market size $20 bn by 2024)
- (Others to follow)

Negative preclinical results for potential re-evaluation:
- Type I Diabetes (Market size $43 bn by 2021)
- Amytrophic Lateral Sclerosis (ALS)

(An analyst note states they, "understand that a majority of Phase IIb patients showed resolution of the arthritis measure (four point score...)".

4) New patent granted in key countries (USA, EU, China, India and Japan) covering Lupuzor up to 2032 and its use in the treatment of a majority of autoimmune diseases such as Sjogrens, rheumatoid arthritis, Crohn's and CIDP. (Announced 27/9/2017)

5) New patent has been filed (2017) to cover non-autoimmune indications. Further preclinical work continues at the CNRS with the objective of further indications moving into the clinic in due course. (Announced 27/9/2017)


Consequently the value of Lupuzor in Q1 2018 should be much greater than $7 billion (potentially multiples).

P.S.
In Mar 2009, HGSi shares (on 50% stake in Benlysta) were $0.45, becoming $3.23 (market cap $528m) early Jul 2009 just before PIII Benlysta results, $12.51 (market cap of $2 billion+) at close on results day late Jul 2009, and $34.49 ($6.46 billion market cap, as there was also some dilution) at peak in Apr 2010 = 76x return over 13 months from peak low to peak high.

[waterloo01] 08/1/2018 15:40

Finncap note: Note upfront and milestones are additional.
Valuation – risk adj. DCF indicates £307m pre-readout value increasing 87%
to £573m (443p per share) on +ve trial results (excludes upfront/milestone
payments which could equal £500m). We initiate with Buy and TP of 237p.

[aussieb3] 08/1/2018 15:32

Jpleight how can u tell how many buys compared to sells