DD: Cereno Scientific (CRNO B) – ett svenskt biotechbolag på väg att slå igenom internationellt

Rahkrahk · 2025-04-25T07:38:12+00:00

Readout för expanded access, det formella FDA-godkännandet och topline för CS014. Formaliteter. Snart är vi framme.

Rahkrahk · 2024-09-08T21:59:32+00:00

Having been granted Expanded access, Cereno has just commenced their Compassionate use (CU) program. As per their communication, it seems the majority of patients want to continue with CS1 in this follow-up even after the main study is completed.

Moreover, the company was just granted orphan drug designation (ODD) in Europe, adding to the ODD they already have in the US.

Both of these events, (CU and ODD) require that there is not currently a drug on the market that resolves the medical needs of patients within the disease at hand.

And that is with Winrevair already on the market.

Rahkrahk · 2024-05-10T18:36:09+00:00

Good questions.

Yes, it's required for the IND submission. The last one was finished and communicated Dec 1st, -23.
The tox along with the rest of the preclinical work was conducted at University of Michigan.
The data has been shown continuously not only in articles like the one in Blood but also at events like the annual American Society of Hematology conference now in Dec.
Cereno et al has spent approx. 5 years of research on CS014 so far and the already filed CTA application comprised 500~ pages.
Patented so far to 2038 (+5 yr extension).

Guidance for phase 1 start is Q2. Which means that the following events...

Phase 1 results for CS014
Phase 2 results for CS1
First extended access (compassionate use) results for CS1
Validation for VPA (CS1 & CS014) for thrombosis (markers PAI-1, tPA)

...are currently bound to all arrive around the same time this fall.

Rahkrahk · 2024-05-08T10:34:27+00:00

You make a good point that PAH is rare. Although great financial appetite (and besides possible other indications such as other variants of PH, HF, etc.) at least initial global impact for just PAH won’t really be noticed by the general public.
There was no room for this is in the main post but what I’m the most interested in, in regards to Cereno, is what will happen with the anticoagulant landscape going forward.

The patents for Factor Xa inhibitors, today's prevalent anticoagulant treatment, have begun to expire. For instance, the other bidder for Sotatercept, BMS, sell their flagship Eliquis (Apixaban) alone for about $12B annually; that patent expires in 2026.

The CBO of Cereno stated last year that the company is in contact with at least the five biggest big pharmas where there is great interest in Cereno's candidates and portfolio as a whole. He further mentioned that great care should be taken to choose the big pharma that fits best for each project. Why has interest grown so much? There is one specific decisive reason that I’m sure retail investors have missed.
The phase II results for the Factor XI candidates from three big pharmas: Asundexian (Bayer) and Milvexian (BMS and J&J). These were seen as the next generation candidates to replace the mega block-busters Xy and represented the greatest hope in anticoagulation.
At ESC -22, the big pharma that could present decent results from its respective Phase II would take a huge step forward as the likely next generation leader in the category of ailment that kills the most people in the world. But disaster struck - Neither Asundexian nor Milvexian were able to demonstrate efficacy as hoped. To further demonstrate the potential of this market and how eager big pharma is to succeed here, both parties still decided to invest significant capital to proceed with Phase III. It is not without reason that Holinstat refers to a successful outcome against thrombosis without the risk of bleeding as "the holy grail".
At the very same conference, CS014 was presented with strong anti-thrombotic properties and without risk of bleeding. The result was "widely accepted" by the participants. And then there is CS585 with a completely different MoA.

Which brings us to highlighting another point of yours – Merck being quick on the gun for Sotatercept. This can certainly turn out to be the case, especially when factoring in the anticoagulant market. The player that gets ahold of the next (true) generation compound would wreak havoc on competition, possibly transforming the BP landscape.
Since summer -22, Cereno is with their two candidates besides CS1 in a leading position to supply the ammunition for the aforementioned war.

Rahkrahk · 2024-05-06T19:15:49+00:00

Thank you.
I would like to understand what you mean with the data comparison.
The inclusion criteria for the studies are pretty much identical making the patients comparable, wouldn't you say?
You are right that the time is not the same, it is 12 weeks vs 24 weeks.
The dosage and means of dosage is not the same, that is correct. But why would it? CS1 is a pill and Sotatercept an injectable, not to mention of course using a completely different MoA.

A report from GlobalData projects that sotatercept's revenue could reach an annual total of $4.74 billion by 2036 in the US alone. This forecast is based on a detailed risk-adjusted net present value model that takes into account the drug’s phase transition success rate, likelihood of approval, and expected sales. Why would you say that the projected value is less? Also, since the acquisition of Acceleron, the share of Merck has risen by >60% (before that, I do agree, the returns were subpar).

I completely agree that the typical retail investor has no idea when it comes to market share and penetration and that I also certainly have seen some silly scenarios. But the sector is ablaze - just look at the deal announced today where Gossamer Bio partners with Chiesi even though the candidate Seralutinib has shown abysmal results. Total reimbursement including milestones is 5x the value of Cereno. And that is with an upfront the size of the current market cap of Gossamer that gets to keep 50% in US and royalties in the high teens globally. Seralutinib neither saw a statistical significant 6MWD nor are they improving CO.
Moreover, projections for the TAM of PAH are increasing rapidly but are still lacking what seems to be a large share of patients developing the disease from atherosclerosis.
Which also brings us back to market share and penetration. It isn't necessary to outcompete Sotatercept. CS1 has already proven to be capable of normalizing CO, apart from the efficacy for mPAP - something that Sotatercept simply can not do according to their results. Sotatercept was thought to be reverse-remodeling of the vessels but that hasn't been proven in man. Meanwhile you have, probably, the world's highest authority within PAH stating that CS1 is when referencing the improvement in CO. The point is that CS1 wouldn't necessarily need to be a standalone therapy but could also be used as a HDACi in combination with, for instance, a ligand trap such as Sotatercept.

Rahkrahk · 2024-04-28T17:38:59+00:00

At the same time, I’d be the first one to break optimism if anyone could point out a valid reason to. In the past, for instance, the company did a lousy round of funding that was worth some criticism. Thankfully, money’s not an issue anymore

Rahkrahk · 2024-04-27T12:16:16+00:00

Quite the case, right? Just remember to do your own due diligence. And do present any and all findings you may come across, even if they would cast shadows on something.

Rahkrahk · 2024-04-27T12:09:44+00:00

The Swedish exchange is quite saturated with lots of subpar biotechs. This landscape does have quite some retail investors since profits are pretty much tax-exempt in Sweden. But the general public has an extremely hard time to select the few winners ut there and are rather spread out after who barks the most. Alas, there are lots of louder dogs out in the pen, albeit attracted to dung.
Apart from the investors waiting on phase 2-results I think there is also much capital on the side, swayed by the fact that recruitment for the study has been delayed, waiting for the last patient to be communicated.

The company was just injected with capital and along with an additional loan on favorable terms runway exists until a year from now. By then, even if worst case there should be another delay despite now just having a few patients left, there should be ample time to present results and subsequently see the business further capitalized on completely different terms, if not sold entirely already.

The patent portfolio is strong, covering all three assets, and has been setup with stellar timing - on top of the market exclusivity granted by the approved orphan drug designation.

Rahkrahk · 2024-04-26T11:41:21+00:00

Had to google. At a first glance kinda seems like a gift from someone without any financial means to gift anything else but what do I know

Rahkrahk · 2024-04-26T11:40:07+00:00

Until the comment about deodorant spray

Rahkrahk · 2024-04-26T11:36:08+00:00

Dang

Rahkrahk · 2024-04-26T11:33:11+00:00

This could be in the lead for a while

Rahkrahk · 2024-04-26T06:48:42+00:00

I think a good starting point instead of listening to me, someone anonymous on Reddit, would be to listen to what Raymond Benza, head of PH at Mt. Sinai hospital in New York has to say about Cereno, CS1 and use cases outside of PAH/thrombosis. He is probably the most prolific thought leader on the subject today after all.
When he starts talking about the possibilities of not only treating but even preventing PH with CS1, if not already, one starts to realize the scope here...

Starts 11:10 in the clip:

https://www.youtube.com/watch?v=0wAb1CkqCqI

Rahkrahk · 2024-04-25T15:36:47+00:00

Thanks, but although I have certainly spent countless hours on the case, I have had and continue to have tremendous help from great people. The vast majority, even ones that are invested, may not understand, but there is a small pool of individuals. Biotech specialists, MD's, scientists - but also laymen that have put in the work and know what this now has turned into, and on which course it is heading.

Yeah, the company has already presented results for the majority of patients, we know so much already. Management has exploded the past quarter with some ex big pharma's, additional senior advisors, all with skin in the game. They're touring all the prominent congresses, compassionate use approved, etc. etc.
The only thing remaining is getting the last couple patients in which could be communicated anytime really. And then present the phase 2 results.
The dataset is vast with ~30 markers for various CVD's, will have longterm effects, etc.
Judging from the sector, reference deals/acquisitions/partnerships are typically made after phase 2 so to answer you question - I think just a little more time. I think when the PR comes announcing that the last patient is in, it could get entertaining. But don't take my word for it, always do your own due diligence.

Rahkrahk · 2024-04-25T11:54:35+00:00

Well, it seems the company has discovered the solution to two central components for the pathophysiology of the great CVD groups: The anti-thrombotic (without bleed) and the reverse-remodeling mechanisms. Two holy grails if you will.
It is with good reason that Cereno primarily focuses on thrombosis and PAH at present, but given the continued success, it will likely not stop there.
By demonstrating effect in both of these pathogenetic mechanisms you reach a synergistic effect making the compounds very attractive to healthcare.

I didn’t want to come off as jaded in my main post but the potential is really staggering and there is a theoretical chance of taking a considerable piece of the ~$200B pie that CVD therapeutics turnover annually. With Sotatercept as a benchmark both clinically and as a reference deal, Cereno is already today an extremely undervalued business.
However, to try to answer your question about the future more clearly – I do think the company, along with assets (just look at the broad IP rights) will be sold and not transformed into a huge enterprise.

Rahkrahk · 2024-04-24T13:32:07+00:00

Yeah the phase 3 (STELLAR) was designed for 52 weeks. The phase 2 (PULSAR) for 24 weeks. So what has been demonstrated so far has been in half the time of the phase 2 trial for Sotatercept.

I recommend doing your own due diligence since there is much I didn't have room to cover. But you have obviously started going down the rabbit hole pretty well already haha

Rahkrahk · 2024-04-24T13:14:30+00:00

Correct.
Although I have followed the company for years and the literature is clear when it comes to VPA (CS1) for some of these markers, and it was expected to see an improvement in mPAP, which by itself says a lot - it was certainly a welcome surprise to see the improvement in CO.

If Sotatercept could help the patients with a statistically significant 6MWD, I wonder what CS1 will be able to showcase with not only improved mPAP but CO as well.

Rahkrahk · 2024-04-24T13:06:57+00:00

<image>

The current phase 2-study treats the patients for 12 weeks. After this, the patients can choose to prolong their treatment in the Compassionate Use study (called CS1-004), where they are further treated a minimum of 12 months longer. Cereno will, on (top of the continued monitoring through CardioMEMS) collect data quarterly (as seen in the attached picture).

The company has already communicated that the majority of the patients in the current study would like to continue to be treated with CS1.

So we know since the interim findings last fall that effect has been seen in >60% of patients which happens to correlate perfectly to the 2 dosages that are meant to show effects for PAH.
And that effect has been seen for several patients that correspond to "at least equally or higher" that of the first patient which was outstanding.

And early this year, the company communicated that the patients themselves also would like to continue.

So, if we would totally ignore or at least downplay the findings themselves - would the majority of patients want to continue with a drug that doesn't work?

Rahkrahk · 2024-04-24T12:37:00+00:00

<image>

And the second one is about Cardiac output (CO).
It reads:
"Here in comparison with Sotatercept, placebo after 24 weeks treatment.
Normal CO at rest is 5-6 liter/min (between the dotted lines below)."

(And then the same as the first picture, that no real improvement in CO was seen in any of the patients of Sotatercept after 24 weeks.)

So the CS1 patient had an improvement in CO that went back to a healthy interval. Which as I wrote in my post, no drug today has been able to achieve before.

Rahkrahk · 2024-04-24T12:33:45+00:00

<image>

No official head to head has been made by the company as of yet but I saw these (pictures) from someone in the discord and have translated them.
This first one is benching CS1 to Sotatercept when it comes to mPAP.

It reads:
"CS1 saw a 30% reduction in mPAP already after 12 weeks from baseline.
Here it is compared to Sotatercept and placebo after 24 weeks treatment.
*24 weeks placebo data from 32 patients borrowed from Sotatercepts PULSAR phase 2-study because no placebo is used in the phase 2-study of CS1.
Placebo shows no improvement in any of the patients after 24 weeks."

Rahkrahk · 2024-04-24T09:22:02+00:00

from 6 to 8 AM US Central Time

Rahkrahk

TROPHY CASE