Eurobench.com

Piddy 21 februari 2022 12:01

1

Lastig parket.

Wat ARWR betreft kan je als belegger zelf je conclusies treffen.
Met wat we dit WE meekregen zie ik geen problemen,integendeel.
Poetin kan ik echter niet doorgronden.
Klein ventje , heimelijk, vangt telkens een vis als hij uitgooit met zijn werphengel ;-)
Ik snap zijn geschiedkundige oerdrang wel met wat hij nu wil realiseren door huidige spierballengerol.

Vermoedelijk ga ik deze week "gespreid" aankopen tot er 225 stuks binnengeharkt zijn, afhankelijk van koersverloop.

Vorige week hoorde ik op VRT een oorlogsdeskundige.
Die verwacht geen grote inval van RU.
Het onverwachtse effect is totaal afwezig (noodzakelijk bij meest geslaagde offensief poging)
Integendeel , wat tik tok filmpjes om het westen wat te imponeren...
Met 190K aan spierkracht is het wel niet eens nodig om onverwachts toe te slaan.

Piddy 21 februari 2022 12:21

0

Vanaf morgen : vandaag presidents day

Hulskof 21 februari 2022 15:23

3

pitstainer is providing some good insight on hif2 on discord. here are some highlights:

from national cancer institute: "How are targets for targeted cancer therapies identified?

The development of targeted therapies requires the identification of good targets—that is, targets that play a key role in cancer cell growth and survival. (It is for this reason that targeted therapies are sometimes referred to as the product of "rational" drug design.)

One approach to identify potential targets is to compare the amounts of individual proteins in cancer cells with those in normal cells. Proteins that are present in cancer cells but not normal cells or that are more abundant in cancer cells would be potential targets, especially if they are known to be involved in cell growth or survival. An example of such a differentially expressed target is the human epidermal growth factor receptor 2 protein (HER-2). HER-2 is expressed at high levels on the surface of some cancer cells. Several targeted therapies are directed against HER-2, including trastuzumab (Herceptin), which is approved to treat certain breast and stomach cancers that overexpress HER-2.

Another approach to identify potential targets is to determine whether cancer cells produce mutant (altered) proteins that drive cancer progression. For example, the cell growth signaling protein BRAF is present in an altered form (known as BRAF V600E) in many melanomas. Vemurafenib (Zelboraf) targets this mutant form of the BRAF protein and is approved to treat patients with inoperable or metastatic melanoma that contains this altered BRAF protein."

pitstainer: "The assumption I have is any of the tumors on this list that express alpha-v beta3 can be targeted by ARWR's alpha-v beta3 targeting ligand"

ici: "What are the limitations of targeted cancer therapies?

Targeted therapies do have some limitations. One is that cancer cells can become resistant to them. Resistance can occur in two ways: the target itself changes through mutation so that the targeted therapy no longer interacts well with it, and/or the tumor finds a new pathway to achieve tumor growth that does not depend on the target.

For this reason, targeted therapies may work best in combination. For example, a recent study found that using two therapies that target different parts of the cell signaling pathway that is altered in melanoma by the BRAF V600E mutation slowed the development of resistance and disease progression to a greater extent than using just one targeted therapy (1).

Another approach is to use a targeted therapy in combination with one or more traditional chemotherapy drugs. For example, the targeted therapy trastuzumab (Herceptin) has been used in combination with docetaxel, a traditional chemotherapy drug, to treat women with metastatic breast cancer that overexpresses the protein HER2/neu."

we know that ca said that aro hif2 is agnostic and combinatorial.

an example from pitstainer of how aro hif2 could work well with a certain patient population:

"Another interesting point here, speculative point, is that 6 patients in cohort 2 were identified to have a form of VHL mutation. 6 patients in cohort 2 were shown to have Stable Disease and and 1 showed Partial Response. I am assuming there is a correlation with VHL mutations responding better to ARO-HIF2a than the non-VHL type tumors. This is implied in the poster material. Screening for the VHL mutation may be a path forward to making ARO-HIF2a "a drug" so to speak"

was the hif2 data a home run? probably not. but aro hif2 is far from dead and buried. in my opinion, aro hif2 showed target response, and relative safety. the fact that the patients were stage four cancer patients with limited life expectancy and all but one made it to the December 1st cutoff date is telling.

for investors, is this drug partnerable? again, I believe that it is. it is, and always was designed as a combinatorial drug.

I believe that phase 2 trial design will examine combinations. I also believe that the drug will be partnered sometime in 2022. as the drug is not currently not valued by analysts, a partnership and a path forward should give the stock a much needed boost.

Hulskof 21 februari 2022 15:25

3

From @pitstainer on YMB I will condense and clarify what tad posted:

1) Poster figure 3 staining showed deep tumor tissue infiltration by ARO-HIF2a at 525mg. This means alpha-v-beta-3 is being targeted effectively. Any cancer tumor -> melanoma, metastatic breast cancer etc. that expresses alpha-v-beta-3, not just renal clear cell carcinoma is a targetable for TRiM Cancer. Exciting validation for the TRiM Cancer platform.

2) Cohort 2 had 6 VHL mutations and 6 or 7 responders. This is not a coincidence because we expect VHL mutants to have runaway HIF2a. Merck’s HIF2a inhibitor is specifically made for VHL type RCC.

Hulskof 21 februari 2022 15:25

4

Reactie BioBoyScout

First off, the patients in this study are not screened for the VHL mutation, so therefore, only around 80% of the patients should, theoretically, respond appropriately to this drug. I don't think there's an issue of targeting alpha-v-beta-3 receptors on the tumor, and that's not something you test for. Alpha-v-beta-3 receptors could also be found on various other tissues in the body, and the drug would also get delivered to those tissues; if the bioinformatics is done correctly, then the target sequence in the drug will not do anything in those other tissues because there's nothing there to knock down. The bigger question is, does the patient have the VHL mutation, and are they seeing enough knockdown of the HIF2a gene (and is it having an impact by allowing the VHL tumor suppressor protein to be activated). So the goal is to knock down HIF2a so that it no longer suppresses VHL, as we want VHL activation (a darn good reason why it takes time for this drug to work and why it's not going to be working for everyone, as proven by the Peleton drug).
We also know that these patients have had numerous other treatments for their cancer. It is known that prior treatments can have an impact on the ability to activate VHL, so this can affect the effectiveness of the drug. We don't know if the HIF2a expression is the primary reason for the cancer, which is why it would make sense to combo this drug.

We do know from this study that there is target engagement. It appears that the alpha-v-beta-3 targeting ligand is getting the target sequence to the tumor like it's supposed to, and that they're able knock down the HIF2a gene. I believe that the ability to partner this drug depends on how effectively (and safely) they're able to knock down the HIF2a gene and reactivate VHL. It definitely looks promising, and would be a great weapon for doctors to have in fighting cancers because of HIF2a (particularly if anemia is a concern, and it usually is).
So will this drug get licensed or partnered? I think it should, and I think it would give the Peleton drug, Welireg (Belzutifan), a run for its money. Come on Chris, show me the partnership.

Tom3 21 februari 2022 21:31

1

Volgens de site van Arrowhead zou de VHL mutatie bij 90% van de patiënten voorkomen. Is het dan niet een beetje vreemd dat van de proefkonijnen meer dan 10 deze mutatie niet had?? De posterpresentatie had het over de volgende indeling:

VHL mutation status, :
- Frame shift
- Missense
- In frame deletion
- No variant
- Not available

"ARO-HIF2 is being developed as a promising new drug candidate for the treatment of clear cell renal cell carcinoma (ccRCC). ARO-HIF2 is designed to inhibit the production of HIF-2a, which has been linked to tumor progression and metastasis in ccRCC. Arrowhead believes it is an attractive target for intervention because over 90% of ccRCC tumors express a mutant form of the Von Hippel-Landau protein that is unable to degrade HIF-2a, leading to its accumulation during tumor hypoxia and promoting tumor growth.

ARO-HIF2 is Arrowhead’s first therapeutic candidate delivered using a new extra-hepatic delivery vehicle.

Disease
Renal cell carcinoma is a type of kidney cancer that originates in the cells that line the small tubes that filter waste material from the blood. RCC is the most common type of kidney cancer accounting for more than 90% of cases with approximately 50,000 diagnoses in the U.S. each year.

Unfortunately, patients with advanced stages of RCC have a 5-year survival rate of only 12-25%. Surgical resection is the mainstay of current treatment while chemotherapy and radiation have not been successful at prolonging survival. The treatment options for patients with metastatic disease are extremely limited.

Clinical Trials
Study Name: Study of ARO-HIF2 in Patients With Advanced Clear Cell Renal Cell Carcinoma
A Phase 1b Adaptive Dose-Finding Study of ARO-HIF2 in Patients With Advanced Clear Cell Renal Cell Carcinoma

ClinicalTrials.gov Identifier: NCT04169711"

Tom3 21 februari 2022 21:59

1

Op de posterpresentatie is bij de check op de VHL mutatie bij cohort 1 (57%), 2 (40%) resp. 3 (46%) no variant of not available. Ik begrijp de uitspraken van BBS dan ook niet zo goed. Waarom scoort cohort 3 niet beter?

ir.arrowheadpharma.com/static-files/9...

Hulskof 22 februari 2022 07:59

2

quote:
Tom3 schreef op 21 februari 2022 21:59:
Op de posterpresentatie is bij de check op de VHL mutatie bij cohort 1 (57%), 2 (40%) resp. 3 (46%) no variant of not available. Ik begrijp de uitspraken van BBS dan ook niet zo goed. Waarom scoort cohort 3 niet beter?

ir.arrowheadpharma.com/static-files/9...

Ik gooi het even op Discord.

Piddy 22 februari 2022 09:03

0

Op Beursig is R.G (beursforum) nu wel echt xxx geworden door zich specifiek voor te doen als beursig.com
Al sinds september 2021 laat hij het forum ARWR aldaar vernietigen met als enige doel zijn ander forum te promoten, wat helaas helemaal niet lukt.

Piddy 22 februari 2022 09:12

0

Benieuwd naar BBS zijn antwoord.
Sommige zaken blijven tot op vandaag toch onduidelijk.

RW1963 22 februari 2022 16:21

0

Vandaag tot nog toe een lichte stijging. Ben benieuwd hoe dat de komende tijd gaat met dat geouwehoer in Oekraïne/Rusland.

nelis h 22 februari 2022 16:30

1

quote:
Piddybull. schreef op 22 februari 2022 09:12:
Benieuwd naar BBS zijn antwoord.
Sommige zaken blijven tot op vandaag toch onduidelijk.

BBS is niet alwetend
zat er met HBV en ENAC flink naast

Piddy 22 februari 2022 16:36

1

nelis , Klopt.
Vandaar dat hij stuk minder snel post vermoed ik.
Ik leerde hem vooral kennen toen hij zijn eigen website knap en erg accuraat onderhield.
Ondertussen is er DSCRD etc.
Op zich kunnen we echt niet klagen waar we de info kunnen gaan lezen voor dit bedrijf.

Piddy 22 februari 2022 18:46

0

C3 Trial updated Feb 21. Start Date changed to Feb. 2, 2022.
clinicaltrials.gov/ct2/history/NCT050...

REEF-D (HBV/HDV) Trial updated today. Clarified/expanded Inclusion Criteria.
clinicaltrials.gov/ct2/history/NCT045...

Ph1 ARO-890 Trial Updated today . Provided citations in the reference section.
clinicaltrials.gov/ct2/history/NCT036...

Credits@Ja-DSCRD

Hulskof 22 februari 2022 21:00

5

www.tickerreport.com/banking-finance/...

Johnson & Johnson acquired a new position in shares of Arrowhead Pharmaceuticals, Inc. (NASDAQ:ARWR) in the 3rd quarter, according to the company in its most recent Form 13F filing with the Securities and Exchange Commission (SEC). The fund acquired 3,260,869 shares of the biotechnology company’s stock, valued at approximately $203,576,000. Arrowhead Pharmaceuticals makes up about 17.9% of Johnson & Johnson’s investment portfolio, making the stock its 2nd biggest position.

Spreekt vertrouwen uit.

Hulskof 22 februari 2022 21:19

1

quote:
Hulskof schreef op 22 februari 2022 21:00:
www.tickerreport.com/banking-finance/...

Johnson & Johnson acquired a new position in shares of Arrowhead Pharmaceuticals, Inc. (NASDAQ:ARWR) in the 3rd quarter, according to the company in its most recent Form 13F filing with the Securities and Exchange Commission (SEC). The fund acquired 3,260,869 shares of the biotechnology company’s stock, valued at approximately $203,576,000. Arrowhead Pharmaceuticals makes up about 17.9% of Johnson & Johnson’s investment portfolio, making the stock its 2nd biggest position.

Spreekt vertrouwen uit.

Hmm, kennelijk hadden ze er al zoveel. Die nieuwe positie was dus gewoon de oude. Negeren maar.

Piddy 22 februari 2022 21:31

0

Dank voor rechtzetting.Bij het lezen dacht ik.Ik koop direct mijn deel maar ik zit al heel de dag te twijfelen( ivm de koersprijs)

mvdln 23 februari 2022 14:33

2

Of we dit serieus moeten nemen valt te betwijfelen, maar ARWR heeft een nieuwe lawsuit aan haar broek omwille van de uitgebrachte Hif2 data. Toch wel straf. Wat is er mis met het publiceren van tussentijdse phase I study resultaten? Je kan al antwoorden waarom CA en consoorten vaak de lippenstijf houden: anything you say can and will be used against you.

NEW YORK, Feb. 22, 2022 (GLOBE NEWSWIRE) -- Pomerantz LLP is investigating claims on behalf of investors of Arrowhead Pharmaceuticals, Inc. (“Arrowhead” or the “Company”) (NASDAQ: ARWR). Such investors are advised to contact Robert S. Willoughby at newaction@pomlaw.com or 888-476-6529, ext. 7980.

The investigation concerns whether Arrowhead and certain of its officers and/or directors have engaged in securities fraud or other unlawful business practices.

On February 17, 2022, Arrowhead issued a press release announcing, “interim results from AROHIF21001, a Phase 1b dose-finding clinical study of ARO-HIF2, the company’s investigational RNA interference (RNAi) therapeutic being developed as a treatment for patients with clear cell renal cell carcinoma (ccRCC).” Although characterizing the results as “positive”, Arrowhead disclosed that “[f]ive serious AEs [adverse events] in 5 patients were reported by investigators as possibly drug related, including myocarditis (in a patient with a history of TKI induced cardiomyopathy), demyelinating neuropathy (in a patient with autoimmune sequelae due to checkpoint inhibitors), chronic inflammatory demyelinating polyradiculoneuropathy (in a patient with distant history of checkpoint inhibitor use), hypoxia (in a patient with a pulmonary infiltrate), and acute hypoxemic respiratory failure (in a patient with progressive lung metastatic disease).” On this news, Arrowhead’s stock price fell sharply during intraday trading on February 17, 2022.

wijzerplaat 23 februari 2022 14:49

0

Pomerantz... Die herinner ik mij nog van Galapagos... sinds toen is het enkel maar bergaf gegaan.

mvdln 23 februari 2022 14:58

4

quote:
wijzerplaat schreef op 23 februari 2022 14:49:
Pomerantz... Die herinner ik mij nog van Galapagos... sinds toen is het enkel maar bergaf gegaan.

We spreken daar natuurlijk wel over iets anders: bij GLPG bleek de FDA uiteindelijk toch problemen te hebben met veiligheidsissues (lobbywerk van Abbvie?). Als je uw grootste potentiële inkomstenbron ziet verdampen heeft dat gevolgen.

CA heeft al geleerd uit het DPC debacle dat je op je passen moet letten. TRiM heeft overigens bewezen zeer doeltreffend, specifiek en veilig te zijn.

Ik vind het overigens wel straf dat een kantoor als Pomerantz een lawsuit begint omwille van deze onderliggende reden. We spreken hier over onderzoek bij stage 4 kankerpatiënten, mensen met weinig of geen levensverwachting. Mensen die verschillende andere lijnen van therapie met zware bijwerkingen hebben gevolgd (die goedgekeurd zijn) en waar ARO-Hif2 bewijst veel minder bijwerkingen te hebben. Bij de patiënten met SAE's wordt zelfs duidelijk omschreven waarom de bijwerkingen zelfs waarschijnlijk (niet zeker!) niet drug related zijn. Ach ja, iedereen moet zijn brood verdienen zeker :)

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