Biotech Pharma Investor

MD. Biotech investing.
SA author.
I also post in X and substack

[Biotech Pharma Investor @Stmkrs]

@richtrades100 ? rs happened already

[Biotech Pharma Investor @Stmkrs]

$SCYX pretty interesting at current valuation
- antifungal pipeline
- new clinical stage asset
- GSK partnership with sales milestones

And trading below cash with runway to 2029

[Biotech Pharma Investor @Stmkrs]

$CING Runway into 2027 and have to resubmit.

Stock not down enough...

[Biotech Pharma Investor @Stmkrs]

$MDNAF I had missed the Sorbie sharing agreement.

[Biotech Pharma Investor @Stmkrs]

@AscendingBio Why are you surprised? Company has been doing this repeatedly

Regular tiny raises at discount

[Biotech Pharma Investor @Stmkrs]

$LSTA...

[Lord_of_Biotechs @Lord_of_Biotech]

This $LSTA Deal is the biggest shitshow I ever witnessed. How can you arrange a new agreement on Friday which will be delayed on Sunday? Who the fuck is making this decisions at $LSTA?
As previously announced, on May 29, 2026, Lisata Therapeutics, Inc. (the “Company” or “Lisata”) and Kuva Labs Inc., a Delaware corporation (“Parent”), together with Kuva Acquisition Corp., a Delaware corporation and a wholly owned subsidiary of Parent (“Purchaser”), entered into an amendment (the “Amendment”) to the previously announced Agreement and Plan of Merger, dated as of March 6, 2026, by and among Parent, Purchaser and the Company (as it may be amended from time to time, the “Merger Agreement”).  Pursuant to the Amendment, the Company, Parent and Purchaser agreed that, upon commencement of the tender offer for all of the outstanding shares of common stock of the Company (the “Offer”) on June 1, 2026, the date by which Purchaser is obligated under the Merger Agreement to commence the Offer would automatically be extended from May 29, 2026 to June 1, 2026, or such other date as may be agreed to between the Company and Parent.
On the evening of May 31, 2026, Parent informed the Company that Parent will not be commencing the Offer on Monday, June 1, 2026, as it previously disclosed and as agreed upon in the Merger Agreement Amendment. Parent has advised the Company that it is negotiating with its potential financing sources and it is evaluating the timing of commencement of the Offer. There can be no assurance as to when the Offer will commence, if at all.

[Biotech Pharma Investor @Stmkrs]

@Lord_of_Biotech Thnx for this post.
Crazy!

[Biotech Pharma Investor @Stmkrs]

@Sports_BioTech1 I.e. there is a risk that cccDNA may eventually come back for the tiny remaining portion.

I think the best chances of cure will come by combining DTIL with treatments (like GSK's) that rapidly elliminate HbSAg. This will allow the immune system to control the last 0.01% cccDNA

[Biotech Pharma Investor @Stmkrs]

@Sports_BioTech1 1. Excellent summary. My only concern is the following. There is no way DTIL therapy can completely eradicate cccDNA. There will be very little left (e.g. 0.01%). What happens with this remaining cccDNA? Will it be controlled by the immune system (persistent HbSAg a problem)

[Biotech Pharma Investor @Stmkrs]

$DTIL Great summary for anyone following DTIL

[Rupert D. @Sports_BioTech1]

I’ve held off on posting my $DTIL thoughts pending the release of additional competitor data at EASL 2026 (more on that below). This has given me time to digest the data, evaluate the field, and form what I express below.

$DTIL EASL update:

Earlier this week, Precision BioSciences stood before the Hepatitis B community and stated that the field is at a turning point. Moving from lifelong suppression toward finite, biomarker-guided viral cure.

The tool that has been developed by $DTIL was designed to target the direct viral source of Hepatitis B, cccDNA — the factory that produces infectious virus, HBV DNA. All drug development to date has targeted things that are downstream from the viral source. This is largely due to there not being a tool (like gene editing with ARCUS in this case) that could get to cccDNA.

As such, the FDA has previously stated in 2022 that sustained suppression (6 months or longer) of HBV DNA (less than LLOQ, TD or TND) off-treatment after a finite duration of therapy is an approval endpoint.

$DTIL declared to the world this week that pgRNA is the appropriate blood biomarker to watch because it comes directly from cccDNA and is the necessary precursor of HBV DNA replication. Note: HBV DNA is undetectable for patients on NAs — all patients in this trial are also on NAs currently.

100% (6/6) patients enrolled in the ELIMINATE-B trial to date who had detectable pgRNA in the blood had pgRNA fully undetectable (eliminated) following the administration of PBGENE-HBV. The fascinating part to me is that it took a varying number of doses of PBGENE-HBV to achieve pgRNA undetectability. In two patients — it took one dose, in three patients — it took two doses, and in one patient it took three doses. Obviously across varying dose levels.

The challenge: if $DTIL is eliminating cccDNA, that will lead to loss of pgRNA in the blood. However, pgRNA is not always detected in the blood. HBV DNA undetectable is an FDA approvable endpoint and so is HBV DNA + HBsAg undetectable. So, what if a patient demonstrates complete pgRNA loss that translates to stopping NUCs with HBV DNA remaining undetectable but HbsAg is still present from iDNA? Does the HBsAg (that has been drastically reduced) still being expressed from iDNA hurt the patient? Billion dollar question right there.

Who better to answer that question than Dr. MF Yuen?

I reached out to Dr. Yuen via email and asked “In your professional opinion, can HBsAg produced from iDNA in a Hepatitis B patient harm them if their cccDNA is eliminated?”

Dr. Yuen responded: “Theoretically, HBsAg produced from iDNA should exert no harm to the liver.”

First & foremost, big thank you to Dr. Yuen for being willing to respond to an email inquiry. The answer received from Dr. Yuen is obviously hedged by “theoretically” because no previously studied tool has been able to eliminate cccDNA like this, therefore this question has not been answered in humans. It seems that Precision will be able to paint that picture at their AASLD update later this year. If indeed this theory translates to practice, this could be groundbreaking.

What about the other patients who did not have pgRNA detectable in the blood at baseline? Another question that must be answered with more research. Dr. Yuen noted during the Q&A session that he “guaranteed” that these patients had pgRNA detectable in the liver at baseline, meaning a biopsy would have had to be the method of detection and measurement here. Is that clinically feasible long-term? No. However, $DTIL will need to get biopsies on patients who are pgRNA- in the blood at baseline and also prove that they are eliminating the pgRNA via cccDNA elimination and correlate that to HBV DNA loss after NA stoppage — exactly what they’ll have to do in the patients with the blood biomarker just with a biopsy.

pgRNA outperforms other biomarkers (e.g., HBsAg) in predicting the effective and safe withdraw of NAs (Terrault NA, et al. J Infect Dis. 2025;231(5):1290-1298.).

The biopsy data:

Two patients (both in cohort 2) have consented to a liver biopsy thus far. Patient 5 (previously disclosed at a high-level) had a pre and post treatment biopsy and patient 6 had a post treatment only biopsy.

The effect of cumulative, repeat administrations were clear. PBGENE-HBV potently eliminates cccDNA which results in loss of viral transcripts. Furthermore, as a secondary mechanism — PBGENE-HBV turns off the polymerase function which results in complete viral inactivation. In plain language, it stops the packaging of pgRNA and shuts down the ability for pgRNA to create new HBV DNA.

Patient 6 (blood detectable pgRNA at baseline) showed full pgRNA elimination in both the blood and the liver which further supports using blood pgRNA as an indication of pgRNA levels and cccDNA in the liver.

Safety:

In vivo gene editing is inherently subject to higher scrutiny because it is designed to alter a human’s DNA. It’s very good to see the LNP related ALT / AST spikes not also increase bilirubin. We certainly do not want a Hy’s Law situation with this program. It was also encouraging to hear Dr. Yuen verbally express that there weren’t any abnormal effects that were out-of-line with LNP delivery noting that the safety profile was “quite OK”.

Despite Cohort 3 having idiosyncratic grade 3/4 AEs, the new simple and mechanism related safety measures have mitigated hypotension and liver lab abnormalities moving forward — this seems that it should continue. Not having to make a “chemistry change” is key here. Some may recall Verve needing to shelve VERVE-101 and move to VERVE-102 to use a different ionizable lipid in their LNP — not the case here.

Next steps:

In summary, liver biopsies in combination with key blood biomarkers reflect cccDNA elimination
and support increased probability of cure after treatment with PBGENE-HBV. I look forward to $DTIL stopping NAs and testing for a cure in the patients with blood pgRNA eliminated first. Although these patients will have to prove 6 months of sustained HBV DNA elimination after stopping the background therapy (NAs), imo, if a patient sustains HBV DNA suppression 1-2 months after NA discontinuation — that is a very good sign because the NA washout period is fairly quick and NAs would be the only other possible suppressor of HBV DNA.

Concurrently, $DTIL will expand the number of participants in cohorts 4 & 5 to try to nail down the best dose combination to take this forward (seemingly as a monotherapy).

The Q&A section, in combination with what a competitor is doing also makes me wonder if $DTIL will explore adding HBeAg+ patients. As a reminder, they are only enrolling HBeAg- patients today. On slide 19 of their presentation, $DTIL also mentions that HBeAg+ patients have higher cccDNA, pgRNA, % of sAg from iDNA, and they verbally mention that it’s an earlier line population that their treatment could potentially benefit earlier and further reduce the change of long-term negative impacts from Hepatitis B. I am fully supportive of starting to enroll people from the HBeAg+ population to continue to PROVE the emerging trend that pgRNA loss in the blood = cccDNA elimination which means that you’ve suppressed HBV DNA.

The partnership piece. $DTIL has stated that they can take this clinical study through phase 2 without a partner. However, I would imagine that there are ongoing partnership discussions in this space. $GSK, $GILD, $RHHBY all natural domestic fits. I am admittedly less familiar with the Asian landscape but would also imagine there are partners based in China that could have interest given the heavy population of Hepatitis B patients in China. $DTIL also including the $GILD logo is no accident.

The readout from $GSK this week vastly beat other currently approved HBV therapies with a functional cure rate of ~19% (still short of the global goal of 30% by 2030). GSK has already submitted Bepirovirsen for approval in the U.S., Japan, Europe and China, with the FDA set to make a decision by October.

Could a Bepirovirsen + PBGENE-HBV be studied as a combination therapy? Bepirovirsen stops DNA replication because it breaks down (doesn’t eliminate) pgRNA, then stops the production of HBsAg, and acts as an innate immune stimulation mechanism. PBGENE-HBV could eliminate the cccDNA while Bepirovirsen takes down the HBsAG — especially if PBGENE-HBV ultimately needs to drive further HBsAg levels. IMO, the reality is multiple treatments working in tandem to cure the disease.

Finally, I have my eye on AASLD TLM in November for a significant update from $DTIL regarding the ELIMINATE-B trial.

Asymmetric competition:

The epigenetic silencing group. Tune Therapeutics had a late breaking oral presentation today at #EASL26. For those who don’t know, Derek Jantz (former $DTIL co-founder & CSO) is now the CSO at Tune after exiting Precision shortly after the Amoroso administration began. Topic for another day but imo he wanted to boil the ocean (they were in food, ex-vivo, many in-vivo research programs, etc.). Say what you want about Amoroso but he has focused the company. I haven’t always agreed with his means of raising capital but the company is now singularly focused on in-vivo gene editing (what they feel they do best) and I respect that. I also digressed a bit.

I’m not going to deep-dive Tune’s data as much as I did for $DTIL.

The approach that Tune is taking to Hepatitis B is a targeted epigenetic silencer that is delivered via LNP (using a guideRNA versus protein recognition like ARCUS). In essence, it is designed to silence cccDNA without cutting the underlying DNA. $DTIL cuts and completely eliminates, Tune silences. When I say that Tune silences it doesn’t remove the cccDNA, it just dresses it in repressive marks (methylation + compaction) The template is still physically sitting in the hepatocyte nucleus, intact, transcriptionally silent but reactivatable in principle. Whereas, gene editing (the $DTIL approach), destroys the template — nothing left to reactivate in the future.

TL;DR on the Tune data: fairly in-line with Precision’s IMO. Though they didn’t achieve the 100% threshold on patients achieving pgRNA undetectability. On the other hand, some of their cohorts only had one dose. Their safety profile is relatively in-line with Precision’s. Durability is a long-term question given the silencing approach versus fully cutting cccDNA. Time will tell. I could see a path where patients select the non-DNA-editing approach if these patients are able to take the next step and discontinue NAs and successfully achieve sustained HBV DNA undetectability. That said, I don’t see Tune talking enough about how this program aligns with FDA guidelines for an approvable endpoint. Time will tell. It’s still early — something to watch.

Before wrapping up the epigenetic silencing topic — Tune has a direct competitor in that space, nChroma, who dosed first patient in January using a similar, if not the exact same, approach as Tune. I believe this company also has ties to the famed David Liu.

I already talked about Bepirovirsen from $GSK. Again something that patients could choose over a gene editing approach. That said, I don’t necessarily view this as competition — rather something that could be used in tandem to achieve a viral cure if $DTIL is unable to get across the finish line as a monotherapy.

Aligos Therapeutics just sold its China rights to their phase 2 HBV treatment. It’s supposed to prevent HBV DNA integration and reduce cccDNA. I just don’t see this as a threat at this time. Good for them getting $25MM from Amoytop in exchange for China rights.

Cash position:

$DTIL had ~$125MM in cash & cash equivalents as of the end of 1Q26. The first quarter of 2026 also saw an earned $7.5MM milestone payment from $TGTX resulting from an azer-cel partnership that $TGTX is using to treat MS and now more.

In speaking to $DTIL leadership late last year, their cash burn is going to be ~$15MM/quarter at the moment.

As we all know, biotechs can be penalized by the market when cash position is too low. I hope this is not the case but I could see a path where $DTIL raises on the back of AASLD data later this year. Let me be clear, I can swallow a raise of $75-100MM @ a $1B valuation, versus a $75MM raise at a ~$75MM valuation (almost precisely what took place last November).

I would hope that $DTIL is actively pursuing mid to late-stage business development discussions to help with the cash position.

DMD program:

Unlike many other DMD gene editing / therapy approaches, $DTIL targets exons 45-55, which account for ~60% of DMD patients. It is one and done and is in-vivo. The best part is that they use a small amount of AAV to deliver relative to competitors and their full capsid ratio is largely higher, they’ve also shown evidence of satellite cell editing in pre-clinical models — driving permanence.

Micro-dystrophin programs have been mediocre to disappointing at best. $DTIL is aiming to create a Becker like phenotype which is ~85%+ of a full length dystrophin. There is an abundance of data to show this type of dystrophin offers functional benefit for humans.

$DTIL has an approved IND and is actively recruiting at Arkansas children’s with a world class expert leading the study from a clinic standpoint.

Where $DTIL goes from here:

The back half of this year remains catalyst rich for $DTIL. They continue to commit to a year end DMD update and we can all pencil in a AASLD TLM update in November for the HBV program imo.

I’ll be honest, I struggle to see the long-term path to independence for $DTIL without going through a series of additional dilutive events. I believe there is a path there for a big HBV partnership that provides sustainable cash to fund DMD to completion. However, I see a path to an exit via M&A starting to form potentially as early as 2027. Build the data story for HBV and DMD, exit to big pharma and use their balance sheet to expand the ARCUS platform to indications that aren’t currently accessible due to capital constraints. Clear path to $GSK, $GILD. $RHHBY would be one of the cleanest fits, imo — they’ve been active in DMD and HBV over the years. $NVS dark horse with past partnerships and a current undisclosed research program.

I’d like to hear thoughts from others as well, don’t hesitate to comment or reach out directly. This is going to be interesting at a minimum.

These thoughts are my own and I state my opinion. I own $DTIL stock. There is a lot of AI slop out there these days — I used AI in research but wrote this myself. I used em-dashes before they were cool.

[Biotech Pharma Investor @Stmkrs]

@milo1234u No cccDNA = no further insertional mutagenesis

But indeed does not solve everything.

[Biotech Pharma Investor @Stmkrs]

@milo1234u @DeenoDino3 They didnt have pgRNA detectable in blood. They definately had in liver

[Biotech Pharma Investor @Stmkrs]

$IONS and GSK should combine their asset with $DTIL. ASO reduce HBsAg + DTIL eliminates cccDNA

[Monaco @monaco_biotech]

$IONS
Ionis partner GSK announces bepirovirsen achieves unprecedented functional cure rates with potential to redefine treatment for chronic hepatitis B

• BioPharmCatalyst https://t.co/x16JxRcYhy

[Biotech Pharma Investor @Stmkrs]

$DTIL just proved they can eradicate cccDNA and market doesnt care??
Next step stop NUCs

[Biotech Pharma Investor @Stmkrs]

$DTIL also "Up to 20% of the doses delivered in the ELIMINATE-B trial have now been administered under the mitigation protocol and no ≥ Grade 3 hypotension events or ≥ Grade 3 LNP-related ALT/AST lab abnormalities have been observed since the implementation"

[avidresearch @avidresearch]

$DTIL

Durable loss of blood pgRNA was demonstrated in 100% of patients treated with PBGENE-HBV (n=6) who had detectable levels pre-treatment (see Figure 3). These landmark results were achieved across four distinct dosing cohorts, providing a clear therapeutic window with multiple paths to be explored through ongoing clinical development. Complete loss of detectable blood pgRNA directly corresponded to undetectable pgRNA in post-treatment liver biopsy, further supporting pgRNA as the appropriate clinical biomarker for assessing PBGENE-HBV effect on cccDNA in the liver. Published literature has demonstrated that loss of pgRNA supports an approximately 10-fold increased probability of cure after discontinuation of nucleoside analog therapy

[Biotech Pharma Investor @Stmkrs]

Completion mid-2027
Topline early 2028
NDA mid 2028

[Biotech Pharma Investor @Stmkrs]

$NGEN (1) Small trial, but placebo-controlled with clinically and statistically significant delta vs placebo

[Biotech Pharma Investor @Stmkrs]

(4) Large TAM, potential to expand to incident population