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Pidbull.
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newsfilter.io/articles/morgan-stanley...

Morgan Stanley Initiates Coverage On Arrowhead Pharmaceuticals with Equal-Weight Rating, Announces Price Target of $41
A21 gobelijn
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quote:

Piddybull. schreef op 9 september 2022 16:44:

Met 4 hadden we een potje kunnen kaarten.
Tot zeer binnenkort...
komt wel van de rog.. nog 1 erbij den ander was er nie denk ik begrijp er niks meer van
Pidbull.
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OP DC (discord) is het gehele analisten rapport van Morgan Stanley geplaatst.

Bull $71 , base $41 , bear $4
harvester
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quote:

Piddybull. schreef op 11 september 2022 12:02:

OP DC (discord) is het gehele analisten rapport van Morgan Stanley geplaatst.

Bull $71 , base $41 , bear $4
Het bull scenario is niet echt enorm maar dat bear scenario is pas echt raar of is dat liquidatie waarde?
Pidbull.
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harvester,
Ik veronderstel dat ook wat want ze gaan er in "bear" vanuit dat echt alles mislukt.
Dan blijft er enkel niks over na enkele maanden.
Hun analyse is een erg lijvig dossiertje maar er is wel meer kritiek over hun waarderingen.
Helaas zitten ze op dit moment ,veilig zoals ze het momenteel uitspelen, vrij raak op.

Euro wordt (deze morgen)iets steviger

De euro wint vanmorgen verder terrein tegenover de dollar. De Europese eenheidsmunt sterkt 0,5 procent aan tot 1,0086 dollar. Daarbij spelen twee zaken een rol: winstnemingen op de Amerikaanse dollar, die afgelopen maand pijlsnel omhoog is geschoten, en berichten dat ECB-beleidsmensen er meer en meer van uitgaan dat ze de rente tot 2 procent of meer zullen moeten optrekken om de hoge inflatie te drukken, ondanks het reële recessiegevaar. Joachim Nagel, de voorzitter van de Bundesbank, zei zondag dat de ECB de rente zal moeten blijven verhogen als het inflatieplaatje ongewijzigd blijft.
Missolapola
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DeZwarteRidder
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quote:

Missolapola schreef op 13 september 2022 07:45:

Arrowhead: Emerging From The Data Desert With A Flood Of Opportunities (NASDAQ:ARWR) | Seeking Alpha

seekingalpha.com/article/4540501-arro...
Arrowhead Pharmaceuticals: Emerging From The 'Data Desert' With A Flood Of Opportunities
Sep. 12, 2022 6:14 PM ETArrowhead Pharmaceuticals, Inc. (ARWR)5 Comments
Summary

Arrowhead is an RNA-interference drug developer with a potentially best-in-class platform in TRiM.
The company has attracted five major pharmaceutical partners in Janssen, Amgen, Takeda, GSK and Horizon Therapeutics.
After a dull 12 months there will be at least 12 clinical data readouts in the next 6-12 months.
There are opportunities for wholly owned assets in liver disease and for billions of dollars in milestone payments in Hepatitis, Cardiovascular, liver and lung.
Arrowhead trades at a ~60% discount to June 2021 highs of $90, yet arguably the company is in a stronger position today.
Looking for a helping hand in the market? Members of Haggerston BioHealth get exclusive ideas and guidance to navigate any climate. Learn More »

Investment Thesis

I have been keeping an eye on Arrowhead (NASDAQ:NASDAQ:ARWR) stock ever since the company first came to my attention in November 2019, after its stock price had hit a peak of $73 - one month prior, shares had been valued at $27, and at the beginning of 2018, less than $4.

It was a phenomenal performance from a company that had recently (in 2016) ditched its lead asset - Heparc-2004, indicated for Hepatitis B - after the FDA placed clinical trials of the drug on hold owing to suspected incidences of liver toxicology.

Arrowhead switched its focus onto subcutaneous and extra-hepatic RNA-interference therapeutics, and its work came to the attention of the Big Pharma Johnson & Johnson (JNJ), whose drug development subsidiary Janssen entered into a licence agreement with the biotech to develop drug candidate ARO-HBV, also indicated for Hepatitis B, and renamed JNJ-3989.
Missolapola
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Vervolg artikel:

Arrowhead received a $175m upfront payment, JNJ made a $75m equity investment, and there are up to $1.6bn of milestone payments written into the agreement, plus tiered royalties on commercial sales, as well as the option for Janssen to develop up to three additional candidates using Arrowhead's Targeted RNAi Molecule ("TRiM") platform, with a further $1.9bn of milestone payments on the table.

The Janssen deal - and to a lesser extent a deal agreed with Amgen (AMGN) in 2016, to develop the RNAi therapy Olpasiran, which involved a $35m upfront payment and a $21.5m equity investment, plus potential milestone payments of up to $400m, provided Arrowhead with the cash it needed not just to survive, but to flourish.

Today, the company is working on a pipeline of 15 assets, mainly targeting diseases of the liver - an easier target for RNA delivery thanks to the development of N-acetylgalactosamine (GalNAc) siRNA conjugates - and lungs. Besides Amgen and Janssen Arrowhead also is partnered with Japanese Pharma Takeda (TAK) on a Phase 2 asset, ARO-AAT targeting Alpha 1 liver disease, GlaxoSmithKline (GSK) on a Phase 1/2 asset, ARO-HSD, targeting non-specific liver diseases, and with Horizon Therapeutics (HZNP), a $3.2bn per annum turnover Pharmaceutical, on ARO-XDH3, targeting gout.
The Horizon partnership is worth $40m upfront and $660m in potential milestone payments, and the GSK is worth $120m upfront and $130m in potential development milestones, plus ~$750m in potential commercial milestones. The Takeda deal is worth $300m upfront, plus potential development, regulatory and commercial milestones of up to $740m.
Missolapola
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Announcing fiscal 2022 third quarter results, Arrowhead revealed it had earned revenues (from its various partner deals) of $212m across the 9m to June 30, but made a net loss of $90.5, with total operating expenses increasing from $184m, to $306m year-on-year.

As I predicted in a note on the company in Jan 2022, however, Arrowhead stock has fallen in value throughout 2022, reaching a low of $28 in June, which is down by >60% from a November 2019 high of $73, when Novartis' $9.7bn acquisition of The Medicines Company - a rival RNAi specialist - led to speculation Arrowhead could also be bought out.

It is also down nearly 70% from Arrowhead's peak price of $90, achieved in June 2021, when the company signed its deal with Horizon, and news broke that Cystic Fibrosis giant Vertex (VRTX) had abandoned development of a drug candidate targeting alpha-1 antitrypsin deficiency ("AATD"), a target for Arrowhead's Takeda partnered ARO-AAT.

Arrowhead's problem is easy to diagnose but harder to fix - the biotech has been making slow progress, which has failed to please either its investors or its big pharma clients. Only one asset - wholly owned ARO-APOC3 - has made it into a pivotal trial, and there have been scarcely any data readouts for investors or clients to pore over in 2022 to date, a fact that CEO Chistopher Anzalone acknowledged on the Q322 earnings call.
We have a large and growing pipeline of clinical drug candidates, providing us with the opportunity to help millions of patients and create a substantial amount of value. It also affords us the opportunity to regularly report clinical data so stakeholders can follow our progress. However, with the development of next generation pulmonary candidates and timing of other studies, we have been in a bit of a data desert over the last several quarters. We are now emerging from that desert.

Anzalone is now promising data - and lots of it across the next 12 months, as follows:

Between now and the end of next year, I expect at least 12 clinical readouts between our wholly-owned and partnered programs. They include the following: one, Biopsy data from the SEQUOIA study in AAT with fazirsiran; two, Phase 1/2 data from ARO-C3 in healthy volunteers and different patient populations; three, Phase 1/2 data from ARO-RAGE in healthy volunteers and patients; four, phase 1/2 data from ARO-MUC5AC in healthy volunteers and patients; five, phase 2 data from olpasiran in Amgen’s LP(A) study; six, phase 2 data from the ARO-ANG3 ARCHES-2 study in mixed dyslipidemia; seven, phase 2 data from the ARO-ANG3 GATEWAY study in HoFH; eight, phase 2 data from the ARO-APOC3 MUIR study in mixed dyslipidemia; nine, phase 2 data from the ARO-APOC3 SHASTA-2 study in severe hypertriglyceridemia; ten, phase 1 data from ARO-MMP7 in healthy volunteers and possibly IPF patients; eleven, phase 2 data from various Janssen studies of JNJ-3989 in HBV patients, and twelve, phase 1 data from Janssen’s NASH study with JNJ-0795.
Missolapola
2
If you are therefore prepared to take Arrowhead's charismatic, ambitious CEO's word for it, and continue to have faith that the TRiM platform is best in class in the RNAi field - superior, for example, to Alnylam's (ALNY), or Dicerna's - acquired by Novo Nordisk (NVO) last year for $3.3bn - this could be a good time to think about picking up some Arrowhead shares.

If, on the other hand, you take the viewpoint that Alnylam, for example, has successfully commercialized five RNAi drugs in the past few years, earning $844m of revenues in 2021, and also acknowledge that new technologies, such as CRISPR/Cas9 gene editing - as developed by CRISPR Therapeutics (CRSP) and Intellia (NTLA) - base editing - as developed by Beam Therapeutics (BEAM) - or MRNA technology - pioneered by the likes of Moderna (MRNA), BioNTech (BNTX), and Pfizer (PFE) - have come to the fore while Arrowhead has toiled in the clinic, you may feel like Arrowhead crown has slipped and its current >$4bn market cap valuation is unwarranted.

In the rest of this post I'll provide some additional colour and context to help investors make up their minds, and offer some thoughts of my own.

Arrowhead Pipeline - Where Are The Blockbusters (and When Will They Make It To Market)?
From a technical perspective, RNA-interference technology works by degrading messenger-RNA carrying instruction to make certain proteins, effectively ceasing production, and "silencing" overactive genes that cause diseases.

Arrowhead's TRiM platform is focused on ligand mediated delivery, tissue specific targeting, and structural simplicity, plus the ability to reach beyond the liver and therefore target a wider range of diseases. Many observers believe TRiM is the best RNA platform available for drug developers, despite the long wait for a first commercialized asset - and in fairness to Arrowhead, attracting the likes of GSK, Janssen, Amgen, Horizon and Takeda suggests that the pharmaceutical world shares that sentiment.

It should be noted that the risk these pharmas are taking is minimal - they are only required to pay out if and when milestones are achieved - but in the ultra-competitive drug development industry, the fact they have opted to work with Arrowhead and TRiM rather than a rival platform must reflect their belief that it offers them the greatest chance of success. We should also note that although Alnylam has five drugs on the market, it has come at a cost - the company's net losses in 2019, 2020 and 2021 were $939m, $828m, and $708m - hardly a business model to try to imitate.

Nevertheless, Arrowhead's only chance of succeeding for its shareholders lies in bringing products to market - and preferably ones that have "blockbuster" potential, i.e. that are capable of generating revenues >$1bn per annum.
As we can see above Arrowhead now has a sizable portfolio of clinical stage assets, but where do the blockbuster opportunities lie?

Beginning with the Takeda partnered ARO-AAT - now referred to as Fazirsiran - I view this as an exciting opportunity. There are four FDA approved products indicated for Alpha 1 Liver Disease - Prolastin-C and Prolastin-C Liquid from Grifols (GRFS), Aralast from Takeda, Zemaira from CSL Behring, and Glassia from Kamada Ltd.

These therapies are "augmentation therapies," which refers to the use of alpha-1 antitrypsin protein ("AAT") from the blood plasma of healthy human donors used to "augment" alpha-1 levels circulating in the blood and lungs of Alphas diagnosed with emphysema - sales data is hard to find, but when was approved in 2010, Prolastin was apparently generating ~$320m of revenues per annum, and controlling 75% of the market.

Evaluate Pharma speculates that Fazirsiran could generate $750m of revenues by 2028, however, with Arrowhead claiming a 20%-25% share. That's due to a broader indication of liver disease associated with AATD, for which there are no approved therapies. Phase 2 data announced in June this year from 16 patients demonstrated median reductions in accumulated total mutant AAT protein ("Z-AAT") at weeks 24 and 48 in the liver of -83.3%, whilst biomarkers of liver injury were reduced while regression of fibrosis of at least 1 stage occurred in seven of 12 patients receiving the 200-mg dose. The drug was also well tolerated with no deaths, discontinuations, of dose interruptions.

As Anzalone noted on the Q322 earnings call, the more important data - 12-month biopsy data - arrives this quarter and ought to be worth paying close attention to. If Arrowhead / Takeda can show that they can genuinely treat fibrosis and reverse liver damage, although the market opportunity may not be initially substantial, the validation of Arrowhead's technology and label expansion opportunities ought to act as a potentially major upside catalyst. Takeda will certainly enjoy a good return on its ~$1bn overall investment.
Missolapola
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ARO-APOC-3 is designed to reduce production of Apolipoprotein C-III - a component of triglyceride rich lipoproteins ("TRLs"), and it's being evaluated in a Phase 3 study in patients with Familial Chylomicronemia Syndrome ("FCS"), and 2 Phase 2b studies in patients with Severe Hypertriglyceridemia.

The only approved drug to treat FCS is Ionis Pharmaceuticals (IONS) Waylivra, which is approved in Europe only, the FDA having declined to do so in the US. Sales are apparently <$50m per annum. Again, it is not so much the commercial opportunity, as the validation of Arrowhead's technology that an approval would bring that matters most to the biotech.

We won't have data from the Phase 3 study until December 2023, but we will have some Phase 2 dyslipidemia data, and severe hypertriglyceridemia within the next 12 months. If positive, Arrowhead could potentially create a lucrative liver disease franchise in time, or better still, one of its big pharma clients could look to make an M&A deal. Speculatively, that could be worth somewhere between the $3.3bn Novo Nordisk paid for Dicerna, and the $9.9bn Novartis paid for the Medicines Company. Let's say $6bn - a healthy >40% premium to Arrowhead's current valuation.

Despite its extra-hepatocellular ambitions, liver is the area that Arrowhead knows best, and the GSK partnership intrigues. The Phase 1 study is now complete, with headline data announced including 9 out of 18 patients experiencing liver fat reductions of 4-41%, and 6/18 patients experiencing reductions in liver stiffness.

The onus is now on GSK to continue development, with Arrowhead eligible for $190m upon a first commercial sale and $590m in sales related milestones and tiered royalties on sales of up to 20%. NASH is a market where there are no approved drugs, due to notoriously strict approval criteria, and this is not an opportunity to bet the farm on, although success in the clinic would be momentous for GSK, let alone Arrowhead.

Into the Lungs, and Elsewhere
Arrowhead suffered a setback with ARO-ENaC2, its first effort to develop a Cystic Fibrosis therapy. Study enrollment was paused last year over concerns about lung inflammation. CEO Anzalone attempted to paint this as a positive during the Q222 earnings call, discussing how the company used the findings to develop next generation candidates, ARO-RAGE and ARO-MUC5AC, which the company is hopeful "can achieve better knockdown with less exposure - the name of the game in RNAi. ARO-RAGE may have a multiple months duration.

Arrowhead released a deep dive presentation for its Pulmonary R&D day, covering both new candidates, which is worth a perusal. The company is targeting asthma, COPD, cystic fibrosis, idiopathic pulmonary fibrosis ("IPF"), and other indication besides. Vertex enjoys near-total dominance in the CF space, and expected to generated nearly $9bn in revenues in 2022. The biggest threat to that dominance is likely to come from a gene therapy, and Arrowhead will want to move these assets into the clinic as quickly as possible.

I also like the look of the Horizon partnered gout opportunity - Horizon has an excellent track record when it comes to driving commercial sales - witness the outperformance (initially at least) of thyroid eye disease therapy Tepezza - and will be keen to upgrade its gout offering, Krystexxa, which generated $140m in sales in Q122 alone. Arrowhead will earn low-to-mid-teen royalties on commercial sales of ARO-XDH, if approved, although realistically, any approval is likely at least 3-5 years away.
JNJ and Amgen

Phase 2 data from the Janssen partnered HBV candidate is arguably the most exciting near-term catalyst that Arrowhead shareholders have to look forward to. Hepatitis B is a 300m patient market, worth >$5bn, and in its Phase 2b study, Janssen said that 19.1% of patients met the primary endpoint of NA stopping criteria, versus 2.2% in the placebo arm.

This seems to be encouraging data, although the ball is in Janssen's court here rather than Arrowhead's as Janssen has full responsibility for development. There will be more data to take in - perhaps as early as November - and this opportunity is arguably Arrowhead's best chance of generating additional milestone revenues in the near term.

The goal here is ultimately to develop a functional cure for Hepatitis B, and Janssen is up against Vir Biotechnology and Roche - via Dicerna - in a race to be first to market. This is simply a huge opportunity for Arrowhead to prove its mettle.
Missolapola
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Meanwhile AMG-890 - now known as Olpasiran - is being rushed into pivotal trials by Amgen after Phase 2 tests revealed a 90% or greater reduction in Lp(A) levels – a biomarker for cardiovascular disease. There's a lot of competition here - from the likes of Novartis and Ionis subsidiary Akcea, Silence Therapeutics and others - once again, Arrowhead's platform will go head-to-head with an antisense (an alternative form of RNAi therapy) drug developer in Ionis. Another great opportunity to validate the TRiM platform.

Conclusion - Data Now Coming Thick and Fast - I'd Back Arrowhead To Achieve One or Two Notable Results
Hopefully this post has given readers some insight into Arrowhead, past present and future. The share price trades at a 60% discount to former highs, yet arguably, the company is in a better position now than it was back in June 2021.

There are several races to market ongoing which Arrowhead and its partners can potentially win. Numerous liver diseases, with wholly owned assets, Hepatitis B with Janssen, and Cardiovascular with Amgen. After a dull but necessary 12 months, the near-term data readouts are beginning to pile up, as CEO Anzalone has pointed out.

The TRiM platform is not perfect and there have been setbacks, but there has also been, arguably, enough positive data readouts to make shareholders believe there can be some notable progression across the next 12 months in genuinely exciting fields of medicine and R&D.

Arrowhead is a little low on cash - $139m at the present time - but CEO Anzalone has indicated that fundraising will not be necessary and will only be done on the back of share price needle moving positive clinical data.

There appears to be a good chance that such data will arrive across the next 6-12 months. There are five major pharma companies heavily invested in the TRiM platform, and although a succession of negative readouts will destroy Arrowhead's credibility and share price - a risk that cannot be ignored, there is certainly a temptation to keep building a position in the company at current low prices.

If you like what you have just read and want to receive at least 4 exclusive stock tips every week focused on Pharma, Biotech and Healthcare, then join me at my marketplace channel, Haggerston BioHealth. Invest alongside the model portfolio or simply access the investment bank-grade financial models and research. I hope to see you there.
Pidbull.
0
Heerlijke samenvatting.

Beseffende dat het dus erg hoog risicogehalte blijft behouden tot de data het tegendeel bewijst lees ik toch ook dat niet fout was om posities te verstevigen in de aanloop van al de gegevens die op ons af zullen komen in de komende 12 maanden.

Gaan die goed zijn dan stijgen we vermoedelijk redelijk fors ,gaan ze 1 na 1 slecht zijn dan gaan we regelrecht naar de $4
Wie dat altijd in zijn gedachte houdt kan zelf bepalen waar hij wil staan in dit verhaal.

Ik vind de uiteenzetting op Seekingalpha op zijn minst zeer neutraal en vrij compleet.

Voetnoot Twitter : Article says $184million, $ARWR actually has $540 million cash
RW1963
1
quote:

Piddybull. schreef op 13 september 2022 12:31:

Heerlijke samenvatting.

Beseffende dat het dus erg hoog risicogehalte blijft behouden tot de data het tegendeel bewijst lees ik toch ook dat niet fout was om posities te verstevigen in de aanloop van al de gegevens die op ons af zullen komen in de komende 12 maanden.

Gaan die goed zijn dan stijgen we vermoedelijk redelijk fors, gaan ze 1 na 1 slecht zijn dan gaan we regelrecht naar de $4
Wie dat altijd in zijn gedachte houdt kan zelf bepalen waar hij wil staan in dit verhaal.


Ik vind de uiteenzetting op Seekingalpha op zijn minst zeer neutraal en vrij compleet.

Voetnoot Twitter : Article says $184million, $ARWR actually has $540 million cash
Als dit, als dat ......... Zo lust ik er nog meer
Wallander
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Piddybull
0
Niks van.
Bekijk eens iets verder het algemeen plaatje...
Alles zakt ivm inflatie cijfers Amerika.
Piddybull
0
quote:

RW1963 schreef op 13 september 2022 18:16:

[...]

Als dit, als dat ......... Zo lust ik er nog meer
Stap je na zo'n opmerking niet beter uit het aandeel?
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