Investing in biotech stocks - My experience so far

BrockStoker

tom9980 said:

Moe_The_Bartender said:

EVFM seems to have other problems.

https://www.marketscreener.com/quote/stock/EVOFEM-BIOSCIENCES-INC-40267487/news/EVOFEM-BIOSCIENCES-INC-Notice-of-Delisting-or-Failure-to-Satisfy-a-Continued-Listing-Rule-or-Sta-36262672/

Nope not a problem at all they can apply for a 180 day extension twice! They can also reverse split to get over $1. I get the feeling they want a dilution first or some unknown to us catalysts exist to get it over $1 such as partnerships. I don't own any EVFM shares for the record.

Yes, agree 100%. This shouldn't be an issue at all. For the record, I intend to buy more if I get the opportunity.

wadsworth101

TY---I am grateful for your work to provide me with the details I wanted. Good luck.

BrockStoker

Heads up. Arrowhead abstract for ARO-HIF2 should be available in about 20 mins. I don't think they'd go to the trouble if the data was not good at the very least. Let's see what the market makes of it..

BrockStoker

Great data, but market not impressed. No surprises there! Glad I opted to buy more AMRS while it was cheap. At least all the recent AMRS buys are in the green after today, and it looks like it may be gathering momentum.

Chris_English

BrockStoker said:

BrockStoker said:

wadsworth101 said:

BrockStoker

It would be interesting, given all your posts about ARWR, what your current balance stands at in terms of overall credit/debit for ARWR ?

I had to crunch some numbers (I hold ARWR in 3 separate portfolios, and at one stage had to sell some ARWR in one, so I could buy back in another due to an over-funding error) so was not aware exactly where I stood with ARWR currently. Here's what I got:

1975 shares cost £67136.38 in total.

Yahoo values them @ £79650.15 after today's close, so £12513.77 gain.

I did manage to buy as low as $21.18 (in March 2020) hence why (along with other buys in the 20's-30's) I'm in the green on ARWR overall, but the 400 Shares bought in 2021 (~$65 average per share) are currently showing a loss of around £3K (-15%).

Of course, weather I'm in the green or red says nothing about the future prospects of a particular company, especially only a couple of years into what I see as a 10+ year investment. That and it's the nature of these types of investment to be volatile. The market has yet to warm to ARWR. If and when that happens, it will be fairly obvious I think.

If you're contemplating buying, there is data due on the 14th, so you might want to dip your toe in now (I would never recommend going all in in your first buy of a stock, especially if you are not experienced with stocks). The share price could go either way of course, but over the long term, at these prices it's a buy IMHO. Please do your own DD, and don't invest what you might need at some point in the future.

That said, I believe ARWR will do very well over coming years, and if an investor is prepared to hold through periods when their investment could potentially drop by 40-50% for significant periods of time, they are likely to do well also, especially if they hold back some cash for when the share price does drop - noting goes up continuously, but stocks like ARWR, AMRS, and even EVFM have *some* degree of safety IMHO at these levels after the pummeling they have all taken. I suspect those investing in the most beaten down of these three (EVFM and AMRS) will actually see the largest gains in the short term, but anything is possible!

Apologies. I went over my sums again as something didn't look right, and realized I'd missed out one ARWR buy of 200 shares.

So the numbers are actually:

Total cost: £75199.49

Actual gain: £4450.73

You seem to be going about this in a really half-arsed fashion if you can miss out trades like this.

You need to sort yourself out, get your records in order, and get a proper understanding of how your portfolio is performing.

You’ve made a few posts suggesting a strong confirmation bias. Combining this with sloppy understanding of your position is a recipe for making bad decisions.

BrockStoker

Chris_English said:

You seem to be going about this in a really half-arsed fashion if you can miss out trades like this.

You need to sort yourself out, get your records in order, and get a proper understanding of how your portfolio is performing.

You’ve made a few posts suggesting a strong confirmation bias. Combining this with sloppy understanding of your position is a recipe for making bad decisions.

It was late at night, and I missed out one buy.

I do keep track of multiple portfolios real time, so I have a good enough idea how they are performing, albeit I don't always add up the totals for all my portfolios. Not sure what counting every penny every day, as you seem to be suggesting, would achieve? It's not like significant movements in the value are going to be "hidden" to me, and day to day movements are mostly noise anyway in the context of long term investments.

If/when needed I can always check my exact position.

BrockStoker

So, going back to the biotech, and recent developments..

Arrowhead recently announced that it dosed the first subjects in AROC3-1001, a Phase 1/2 clinical study of ARO-C3 for various complement mediated diseases, and completed enrollment in the Phase 2b ARCHES-2 clinical study of ARO-ANG3 for mixed dyslipidemia. It's patent for EPAS1-related diseases was also accepted yesterday, and I think it's worth drawing attention to, in particular, this section from the abstract:

"The present disclosure relates to methods of treating EPAS1-related diseases such as cancer, metastases, astrocytoma, bladder cancer, breast cancer, chondrosarcoma, colorectal carcinoma, gastric carcinoma, glioblastoma, head and neck squamous cell carcinoma, hepatocellular carcinoma, lung adenocarcinoma, neuroblastoma, non-small cell lung cancer, melanoma, multiple myeloma, ovarian cancer, rectal cancer, renal cancer, clear cell renal cell carcinoma (and metastases of this and other cancers), gingivitis, psoriasis, Kaposi's sarcoma-associated herpesvirus, preeclampsia, inflammation, chronic inflammation, neovascular diseases, and rheumatoid arthritis, using a therapeutically effective amount of a RNAi agent to EPAS1."

You can see that this one patent/target/drug *potentially* opens the gate to multiple indications. It can be trialed for one indication, ie. phase 1 + phase 2 + phase 3, and if successful (FDA approval due to good/great safety and efficiacy). for all the other indications it will only need phase 2/3 trials since safe dosage has already been determined. Arrowhead will be able to run many more parallel trials compared to it's non RNAi peers, while not having to spend as much per indication - win win! Fast, efficient, and able to punch way above it's weight. The share price does not reflect any of this, as usual!
All of this is with a backdrop in the sector where at least some of the competition (CRSPR connected biotechs like NTLA) is currently suffering setbacks in the form of patent woes, but that seems like a small problem compared to the other issues CRSPR has.

Amyris reported Q4 earnings, confirming it's growing revenue at a fast pace and is guiding to be profitable by EOY. The share price response has been muted (so far) but positive. It's partner ImmunityBio reported very encouraging results for it's bladder cancer trial, which IMHO bodes well for it's joint venture with Amyris. Although I'm not exactly sure what tech they are using, it seems to be working, so I'm considering opening a small position to hedge my bets. Still not quite sure what to make of the CEO though. Going back to Amyris, I think we've seen the bottom, and it will gradually head back up to where it was a year or so ago.

Lastly, Evofem has been slowly but surely going up since the start of the year. It's one to watch over the next few hours as earnings are due and the expectation is for 1,970.6% YOY growth in revenue.

The main question for me now is, what will I be able to pick up for my limited budget in a few weeks time?!

BrockStoker

I've managed to do it again - I neglected to post one of the most important bits of news for Arrowhead that has recently broke, and it's VERY encouraging IMHO. The abstract is still embargoed but we have the title:

"Silencing Muc5ac Expression with a Lung-Targeted RNAi Trigger Prevents Allergen-Induced Mucoobstruction and Airway Hyperresponsiveness"

That title strongly suggests that it works, otherwise it would be very misleading. It's also HUGE in terms of indications and potential revenue.

Also worth mentioning, is that, along with Muc5ac, another potential BLOCKBUSTER for ARWR, ARO-ANG3 is looking like a stronger candidate in the race to corner the cardiovascular disease market, after Phizer said it was out of the race. It's looking like it's a two horse race between Arrowhead and Regeneron now, and my money, as always, is firmly on Arrowhead.

So the pattern of competitors falling at the way side continues, while Arrowhead forges ahead, continues. It continues not due to chance, but by design - because the science is good. I plan to continue adding to my position while the market completely dismisses ARWR's potential and misinterprets what it has already achieved.

BrockStoker

New ARO-Hif2 abstract just published, strongly suggests POC for RNAi outside of the liver as well as POC for the targeting of tumors specifically. It also strongly suggests Arrowhead has a cancer franchise. It's early days, but we now know it's efficacy is good at the very least, and we know it's safe, so other potential issues aside, there's no reason the FDA is not going to approve it IMHO. The market on the other hand looks like it will wait for phase 3 data or even approval before it rewards share holders fairly! Same old story. In the mean time I still hold hope that the markets get excited over one (or more) upcoming catalysts, perhaps even something none of us are expecting, and fully intend to buy more ARWR in a few weeks.

Here's the abstract text, with a few parts I've highlighted/bolded.

"Targeting HIF2a with siRNA: From preclinical models to the clinic

Hypoxia-inducible factor 2 alpha (HIF2a) is arguably the most important driver of kidney cancer. HIF2a is constitutively activated following von Hippel-Lindau (VHL) gene inactivation, the signature event of the most common type of kidney cancer, clear cell renal cell carcinoma (ccRCC). HIF2a functions as a heterodimeric transcription factor and regulates a program of gene expression that promotes cell proliferation, stemness, and angiogenesis. Using a highly specific inhibitor designed to target a structural vulnerability in HIF2a (PT2399), we previously showed that approximately 50% of ccRCCs are dependent on HIF2a. However, prolonged drug exposure results in resistance and the acquisition of gatekeeper mutations, which we reported first in patient-derived xenografts (PDXs) and subsequently in humans. Using the same PDX platform that previously validated PT2399, we show that HIF2a can be effectively inhibited using a tumor-directed siRNA (siHIF2). Referring herein to both first- and second-generation (ARO-HIF2) siRNA drugs, siHIF2 is specifically taken up by human ccRCC tumors transplanted in mice, where it depletes HIF2a inhibiting target gene expression and tumor growth. Through orthogonal RNA-seq studies integrating both PT2399 and siHIF2 in PDXs, we provide unprecedented detail on the HIF2a effector transcriptome, which we further dissect by incorporating ChIP-seq. A PDX line was generated from a ccRCC patient who had paraneoplastic polycythemia (a HIF2a dependent syndrome due to erythropoietin [Epo] secretion by the tumor) and participated in the phase I trial of ARO-HIF2 (NCT04169711). We show that siHIF2 effectively depleted HIF2a in both the PDX as well as in the patient, that it normalized Epo (and hemoglobin), and that it inhibited tumor growth. siHIF2 has activity against both wild-type and drug-resistant mutant HIF2a and is expected to be active in patients progressing on PT2977 (belzutifan), a PT2399-related drug recently approved by the FDA. To our knowledge, this is the first example of functional inactivation of an oncoprotein with a tumor-directed siRNA in humans. In summary, these studies provide unique insight into HIF2a (the only known core dependency in ccRCC), illustrate how it can be effectively inhibited by an siRNA drug, and establish a paradigm for the development of tumor directed siRNA-based therapeutics."

Note that "50%" part I've bolded above. I believe it explains the disappointingly low sounding overall response rate of the trial of 39%. It implies the actual response rate (if you only include the 50% of ccRCCs that are dependent on HIF2a) should be *closer to* 39% x2 = 78%

coastline

The case for going up ? See what happens with the Fed and rates today but chances are it'll be 0.25% up for a start.

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