Corvus Pharmaceuticals Inc (CRVS) News

CRVS 10Q due 3/19

CRVS under $2

CRVS............................................https://stockcharts.com/h-sc/ui?s=CRVSS&p=W&b=5&g=0&id=p86431144783

CRVS................................https://stockcharts.com/h-sc/ui?s=CRVS&p=W&b=5&g=0&id=p86431144783

CRVS under $2

Reversal plays are back.

mb

CRVS under $2

The best way forward for Corvus is to find a partner who is interested in taking soquelitinib (formerly CPI-181) into the much bigger therapeutic area of autoimmune diseases and take half of the rights of the molecule. Richard should negotiate for a sufficient upfront payment to cover the costs to complete the n=150 patients Phase 3 registrational clinical study in PTCL that the FDA as agreed with. Randomized the 150 patients to 1:1 to soquelitinib vs standard-of-care that see patients with only PFS of about 3 month, the trial should be fairly quick (less than 3 years, maybe 2 years). There should be plenty of mid and big pharmas who would be interested. No dilution, please, Richard. It's not worth it.

Yes, I’ve read that book. And having worked in the Bay Area biotech industry for over 20 years, you can’t help but know many of the players. Duggan got into Pharmacyclic by dumb luck, driven by the death of his son from glioblastoma. Duggan was attracted to Pharmacyclic by the failed drug motexafin gadolinium, but he was smart enough (viciously) to pivot to supporting ibrutinib. Miller lost credibility with Wall Street and control of the company due to his decade long fixation on that failed drug, culminating with his writing of that nasty opinion piece of the FDA for The Wall Street Journal. Persistence can be a double-edged sword sometimes. Miller is academically brilliant, but he was too stubborn to adapt to changing conditions. So he missed out on the windfall for both rituximab and ibrutinib. Roche ate his lunch on the former, Duggan on the latter. Let’s hope he has learned his lessons and adapt to reap the windfall of CPI-818. Two strikes, and this point in his career, he’s at bat with full count. Let’s see if he can get a hit, or if someone needs to step in to make the first ITKi successful.

Hopefully Miller has his payback and glory from developing another blockbuster CPI818z.
What a great movie For Blood and Money would make.

If you read the recent book “for the blood and money”, you will find out that Miller actually had given up on motexafin gadolinium. He was starting the process to develop btki which they had licensed from Solera. At this point Duggan took control of pharmacyclics and insisted on not giving up on motexafin gadolinium. Duggan also replaced the board. Miller lost all control and resigned from the company and sold all his pharmacyclics stock and options. But duggan realized his mistake later on and hired staff to start the btk work. Miller was the brainchild of btki and he was the first one to know its potential. But he unfortunately didn’t benefit from the success of the drug and the pharmacyclic stock.

Corvus price action acting like CPI818 failed a phase3 trial. Will add next week.

CRVS.......................https://stockcharts.com/h-sc/ui?s=CRVS&p=W&b=5&g=0&id=p86431144783..

I don't know about accumulation. I've been buying this stock since 2018 when they announced the only ITKi in the clinic, CPI-818. I won't pretend to be able to predict stock price movement. Personally I assigned zero value to their A2A inhibitor or anti-CD73; but that's just me. I'm a molecule guy; I follow the molecule, and CPI-818 is shaping up to be one hell of a molecule, after almost 5 years of waiting and meandering in Phase 1a, finding the dose and understanding its mechanism of action. I'm also heartened that it appears that Richard has learned his lesson from his debacle at Pharmacyclics, where his stubbornness and refusal to let go of the failed motexafin gadolinium led him to lose control of the company and the first BtKi that was the mega blockbuster ibrutinib; it appears that he's now prioritizing CPI-818 over everything; about time.

IF it's true what Richard said regarding CPI-818 specificity regarding its ability to differentiate between ITK and RLK (the difference being only amino acid between these two related kinases), then this molecule will have a huge potential in autoimmune diseases that originate from Th2 dysfunction. That alone is a mega blockbuster, $20bil+.

IF the skewing of lymphocytes toward Th1 (the killer cells that eliminate cancer cells and viral infection) is the mechanism of action of CPI-818, and we see similar objective response rate in solid tumors for patients with ALC > 900 or who have normal ALC of 100-4000, then this molecule will be used with every approved drugs in solid tumors. That alone is a mega blockbuster. Potential value there is unprecedented, off the chart. Corvus is planning to start a Phase 1 study with CPI-818 (I'm assuming at the optimal dose of 200mg twice daily) as early as this year, so we won't get that glimpse of initial clinical data until late next year at the earliest, if not mid 2025.

Great news for CRVS. Options were heavy on the call side.

$4s came quickly with more to go. Accumulation stirring.

mb

Latest update from Jefferies Healthcare Conference

Alright, if you've been following, what has changed from April corporate update to yesterday update at Jefferies?

Before I post the latest update, for context, here are the registration studies for the two currently approved agents for relapse/refractory T-cell lymphoma (R/R TCL) and some common terminology: ORR or objective response rate means partial response + complete response (PR+CR); progression free survival (PFS); absolute lymphocyte count (ALC) per microliter. Remember that in this aggressive disease, many patients don't even make it to the first evaluation period (for CPI-181, that is 3-month of treatment) since they have about 3 prior treatments before taking CPI-818. So, it is critical to illustrate the activity of CPI-818 to include less sick patients, where their ALC is still normal (>1000).

-pralatrexate (in 111 patients): ORR of 29% (with CR of 11%), PFS of 3.5 months
-belinostat (in 129 patients): ORR of 25.6% (with CR of 10.6%), PFS of 8.4 months

April 2023, Corvus reported for CPI-818 (13 evaluable patients, with n = 8 patients meeting Corvus biomarker criterion of ALC>900, data cutoff as of February 20223): ORR of 4/8 or 50% (with 3/8 or 37.5% CR), PFS of 28.1 months; for patients not meeting their biomarker criterion or ALC<900): ORR of 0/5 or 0% (with 0/5 or 0% CR); PFS of 2.1 months

June 7, 2023 Jefferies conference, Corvus reported for CPI-818 (19 evaluable patients, with n = 13 patients meeting Corvus biomarker criterion of ALC>900, data cutoff as of May 1,2023): ORR of 6/13 or 46.2% (with 3/13 or 23% CR), PFS of 19.9 months; for patients not meeting their biomarker criterion or ALC<900): ORR of 0/6 or 0% (with 0/6 or 0% CR); PFS of 2.1 months

The data that will be presented next week June 13th at the iCML in Lugano, Switzerland won't be much different from the June 7, 2023 presentation; maybe a couple more evaluable patients will be included and some of the stable disease patients could convert into PR or PR into CR, but that's it. It won't materially change the ORR and PFS from yesterday's presentation.

Richard Miller (Corvus' CEO) also further clarified on their planned registrational phase 3 study for CPI-818 in R/R TCL (Richard expects to meet and conclude meeting with the FDA before August 2023) that will also enroll less sick patients (with one and three treatments; to take advantage of CPI-818 mechanism of action of skewing toward Th1). The trial will be 1 to 1 randomized study with 75 patients in CPI-818 and 75 patients with the physician's choice of either pralatrexate, belinostat or gemcitabine (which is not an approved drug, but it's an old drug and oncologists used it more than pralatrexate plus belinostat combined), with PFS as the primary endpoint; with PFS in the comparator arm (pralatrexate, belinostat or gemcitabine) expecting to be about 3 months, the trial will be completed and NDA filed in 2.5 years from end of this year.

CRVS beginning to firm up as the $4s are in sight.

Can't wait for the sudden pop.

mb

Oh yes. This huge

big pr 9min ago,THINKING ABOUT BUYING,these can skyrocket tickers for days/weeks,really GOLDEN now imo

institutional buys increasing,could see big push higher as gaining followers too

1 of 4 golden crosses in big boards,others lousy with low vol.,CRVS is really GOLDEN

Blockbuster company.

CRVS getting attn.

mb

CRVS in Compliance w Nasdaq requirements.

https://app.quotemedia.com/data/downloadFiling?webmasterId=90423&ref=317420846&type=PDF&symbol=CRVS&cdn=8b04f14c9e2d1c64ebccb4bc39e0ffde&companyName=Corvus+Pharmaceuticals+Inc.&formType=8-K&formDescription=Current+report+pursuant+to+Section+13+or+15%28d%29&dateFiled=2023-04-24

FL

Interesting D&D. BioNTech is very well connected, and they do seem to be working around the same space. I could definitely see some interest there. I just hope CRVS can develop 818 far enough to raise money the share price in order to negotiate decent terms for any kind of partnership or buyout.

Crescendo and Biontech appear to be targeting the development of novel, targeted T cell enhancing therapeutics for treatment of cancer. BionTech looks to be exploring several approaches " mRNA-based therapies, innovative chimeric antigen receptor T cells, bi-specific checkpoint immuno-modulators, targeted cancer antibodies and small molecules".. They are in early clinical trial for prostate cancer..

I wonder to what extent CRVS has crossed BionTech's radar. Looking at the links it looks like Biontech has collaborations with Genmab, so monoclonal antibody approaches to T cell modulation have to be high on their list.

FL

https://finance.yahoo.com/news/angle-plc-announces-pharma-services-060000021.html

https://investors.biontech.de/news-releases/news-release-details/biontech-and-crescendo-biologics-announce-global-collaboration

$CRVS accelerates clinical progress of CPI-818 in the U.S. after Angel Pharmaceuticals begins clinical study of CPI-818 in China. I think the clinical studies of Mupadolimab will have the same development pattern.

First line will be different and more derisked than R/R.
R/R : goal is an approval of 818 as MONOTHERAPY by achieve orr 25-30% and mDor > 6 MO
1s line : goal will be approval of 818 as a COMBINATION with CHOEP. Regarding the different kind of moa between these two treatments, we could anticipate in derisked manner and with confidence that if 818 will be approved in R/R as monotherapy, drug will be approved in 1st line to.
This is why I think it is a 2023 story.

First line will be different and more derisked than R/R.
R/R : goal is an approval of 818 as MONOTHERAPY by achieve orr 25-30% and mDor > 6 MO
1s line : goal will be approval of 818 as a COMBINATION with CHOEP. Regarding the different kind of moa between these two treatments, we could anticipate in derisked manner and with confidence that if 818 will be approved in R/R as monotherapy, drug will be approved in 1st line to.
This is why I think it is a 2023 story.

I agree on institutions with this volume. I have wondered whether Corvus cancelling their shelf with Jeffries was part of something deeper going on. Maybe they got wind of Jeffries manipulating the stock downward, or maybe they felt Jeffries simply was not capable of supporting the price properly for an offering, so Corvus signed on with another investment firm to handle an upcoming placement. Part of the deal was for the firm(s) involved to bring the price up to an acceptable level first.

If I were Corvus and the board, I would be working behind the scenes on something like that. Combine institutional support with 818 news and talk of an upcoming phase 3 discussion with the FDA, and suddenly you're able to sell 20 million shares at $5 instead of 75 cents.

Up more than 20% on 12X volume. Looks like institutional investors are taking notice!

FL

Agree. To me, this is an extremely bullish sign. I hope it is to institutional investors as well.

Miller cutting his compensation in lieu of stock option based comp speaks strongly as to where he thinks CRVS is headed,

FL

Loving the aftermarket price action. Should open up nicely tomorrow. Great start to the week today.

Bill,
IHUB Biotech Values is also a good board for for less company specific Biotech discussion. I tried posting this on Yahoo but it was censored and restricted.

FL

Thanks MyBio. I think we're all in agreement that the refractory pool bar is a heck of a lot lower. It certainly seems to me that the path to approval in that indication is pretty clear, barring any late and serious safety signals (which seems unlikely both due to them not seeing any yet, and the MOA).

What do you think about the bar to clear in frontline re prior messages?

So anything over 30%orr and 6mo duration of response will be a big win.
So far, with and without ALC biomarker use, the data of the first 13 patients beat these bar.
At lugano meeting, only early data of 7 patients recruited will be presented : I would like to see DCR > 50% with 1-2 response and 1-2 stable disease.

Temperate your expectations in R/R PTCL : ORR 30% mDoR >6 months are the bar to achieve.

I am crvs shareholder to and follow the company and 818 dvpt since several years.
The early data generated so far are excellent and much more strong than current soc in R/R ptcl.
The goal to achieve for the 7 new patients is not to maintain current data but to demonstrate patients interest and competitive value. Physicians expectations in this setting is to have a safe drug with ORR > 25-30% and duration response > 6 months.

Good conversation you two are having. Most of it well above my pay grade. However, without the same grasp of details, I was also arriving at a similar big picture scenario. Continue IB with patients with ACL>900 and update results in Lugano in June and then hopefully the data lines up for the Phase 3 registration trial mtg with FDA with fast track Orphan drug status.

CAR-T Gene therapy was mentioned in the prior posts as a possible competing treatment for PTCL. I believe Miller really took a few shots at this line of treatment in one of his previous presentations. If CAR-T does show promise and make it to market, I doubt that this treatment would be priced less than $500,000.


Given the difficulties treating PTCL and the relative rare occurrence rate. I agree w the 8K annual estimate in the US based on the following:
https://acsjournals.onlinelibrary.wiley.com/doi/10.3322/caac.21589
Given this limited US market, I can see the FDA-Orphan drug pathway as reasonable shot. I have no idea how it would be priced. $150K is certainly consistent w other life saving treatments. If trials are successful, I would also assume that the emphasis would shift to front line treatment or combo in order to reach patients before their immune response is degraded by Chemo.

Thanks for the discussion.

FL

Top line data for the 7 patients with ALC > 900 should be available and presented at the ICML conference mid June. Until then, there will be lots of volatility in CRVS. Hold on to your panty hoses. And shortly thereafter they should have that meeting with the FDA to discuss the registrational randomized Phase 3 study; if the data confirm the blocking of Th2/Th17 and skewing toward Th1 hypothesis, which requires patients to have ALC > 900 to be responsive and beneficial on treatment with CPI-818, then the share price should appreciate to the $10’s by end of the year for them to raise much needed fund to complete the registrational Phase 3 study. Partnership with a big partner could also work, if the financials make sense. With the kind of data in refractory PTCL that would be competitive with CHOP in frontline, hedge funds will jump into CRVS. That should be fun for all CRVS longs. Any potential application in autoimmune like atopic dermatitis can be pursued once CRVS has a far better financial health.

I agree. I think we have one last major hurdle to go, and it's those new ALC>900 patients on study right now. They need to confirm that kind of initial response rate. If they do, and side effects remain low, we've got a clear runway for an orphan drug designation and fast track status for a registration trial in refractory PTCL--likely early next year. And then they look at frontline in subtypes most likely to respond. By then, I hope they have raised enough money at much higher prices (or have landed a partnership) that it allows them to explore 818 in autoimmune.

If what Richard is saying is verified with the 7 remaining patients currently on study, who were selected based on the additional criterion of their ALC having to be above 900, if the response rate in patients with ALC > 900 is about 80%, and the CRs rate is 40%, which also indicated that SD/PR patients have a chance of converting into CRs on treatment for refractory PTCL, then yeah, CPI-818 might very well be competitive with CHOP in the frontline setting as well. CHOP is brutal on your immune system. If you have a normal ALC level (around 4000), I would opt to take CPI-818 first, especially if you’re positive for Th2/GATA3, which has poor prognosis for survival, and the hypothesized mechanism of action of CPI-818 seems to be blocking Th2 and Th17 and skewing toward Th1. After refractory PTCL, maybe the fastest path to frontline PTCL is through subset of patients with positive Th2/GATA3. And then position CPI-818 as second line behind CHOP for patients who progress or become lymphopenic (ALC level dropping below 1000). And then do the CPI-818/CHOP combo for all front line study.

I think the frontline setting is a lot tougher. From what I can tell, CHOP and BV-CHP approaches have 80%+ response rates and 40%+ complete remission rates lasting for years, and even some cures, at least in certain subtypes of PTCL. Then there's CAR-T therapies in trials right now--while more risky in terms of side effects, they have very high response rates. All this means I think 818 would have to have eye-popping responses as a mono therapy in a frontline setting.

I wonder if 818 might carve out a market in frontline combo therapy. If it's very well tolerated and it's mechanism of action is in fact doing what Corvus thinks it is, it might make existing treatments even better. CHOP-818?

Good back of the envelope calculation for the third line PTCL. But if the hypothesis on CPI-818 mechanism of action is correct, that you need a healthy normal ALC number, then the front line setting will make this a multi-blockbuster. Never mind the fantastic wet dream of CPI-818 also working in solid tumors. Somebody really should forward the CPI-818 data to Bob Dugan or Wayne Rothbaum because Miller just got lucky again, but he still hasn’t learned his lesson about focus and value creation.

I agree; I’m not confident in Miller’s business acumen at all. We need another Bob Duggan to take over. I’ve been following Corvus for a long time. And I know Miller’s weakness well: his tendency to stay with molecules to their bitter ends. I’ve been waiting for data on CPI-818 since 2018. He needs to scrap everything and focus on CPI-818. He will be making the same mistake with CPI-818 that he made with ibrutinib with Pharmacyclics. Nothing in Corvus has any value beside CPI-818. Bob Duggan to give up on his dream of making money with antibiotics at Summit and come take over Corvus.

Looking at refractory PTCL market size, which appears to be the initial indication and quickest path to approval for 818. PTCL cases are between 5-15% of NHL annually, which works out to roughly 4,000-12,000 patients a year (I believe this is US only and the incidence worldwide is almost double, but I may be wrong). Let's say 8K US for this back of the envelope. Most of them will eventually progress. If you figure the refractory cases are about 70% a year, that's an initial patient pool of about 6,000. Corvus has said they believe about 70% have ACL levels at 900 or above. So that's 4,200.

One thing I'm not certain about is whether 818 would potentially treat all PTCL cases with ACL over 900, or only some of the PTCL subtypes. But for this calculation let's consider all of them. Orphan drugs for small populations command a high price point, so let's say Corvus charges $150,000 per patient. Total market would be 630 million.

Of course they're interested in expanding to other indications, and then there's the potential auto immune market, which is huge. But this indication alone, even though small, could support eventual annual sales of 250-500 million and a market cap between 1-2 billion in my opinion. This make sense? Any major mistakes here?

Kenyon

I think you' re correct, Early clinical trial studies being done by companies with little wherewithal to last to late stage trials are being valued at 0. That is why CRVS trades at less than cash. I have bar-belled a portion of my portfolio to include these cheap lottery ticket speculative stocks such as CRVS. On the other side I maintain long term dividend paying stalwarts.

FL

Well, they started enrolling in early February I believe. Since it's the Kidney Cancer Consortium and happening at MD Anderson, and it's first line disease, I'm assuming they'll be able to get patients enrolled fairly quickly.

Phase 1B is only 15 patients, stage 4 metastatic RCC patients with no prior treatments are eligible. This is a pretty sick pool. They're going to be looking for increased ORR over standard of care. My rough guess is that if the combo works they way Corvus hopes it does based on the way it looked in preclinical, with no serious safety flags, we'll start hearing about that by early fall.

I don't think investors are giving Corvus any value for this right now. That could change in a hurry.

I don't have any idea what the relative timing is for the KCC ciforadenant trials.
But definitely worth keeping an eye on it, as well.

I suspect the Angel trials will also be altered to enroll based on participant ACL levels.

Have a good weekend.

FL

Initial results from the frontline RCC combo trial with the kidney cancer consortium. I see that as a total wildcard but if they start seeing eye popping results, and in an open label trial like that it could happen quickly (the preclinical studies were impressive, but of course that’s a different ballgame than in humans)—then sky is the limit.

Upcoming Catalysts for CRVS.

1) AACR presentation on 818 in Mid April;
2) ICML presentation in Lugano in Mid June;
3) Top Line data on ongoing Angel Phama trials in China;
4) Meeting with FDA to design the 818 Phase 3 Registrational trial;
5) Announcement of a Big Pharma partner for Clinical Trials??????

Any others I'm missing. For some reason Yahoo blocks this content.

FL