Telix Pharma (TLX AU) - TLX591 trial
Californication
There is a big fat disclaimer at the rear of this post - read it. This is not financial advice, and is merely my honest and genuine analysis on the securities discussed.
Previous writing on TLX AU can be found here.
Setup: PT upgrades and buying on valuation/tariff-selloff/market share gain stories that are all bullshit. NTM the defining factor are TLX591 p1 ph3 readouts due 2H25.
What we have is sellside pushing and buyside generalists long into Ph3 RCT trials where it appears no one has done any substantive work. Without being highly convicted, I am bearish.
Necessary understanding: TLX591 is derived from Huj591. It is radioligand prostate cancer therapeutic that using a monoclonal antibody. If approved, it would hypothetically compete with NOVN’s FDA-approved Pluvicto, which uses a ‘small molecule’. In simple terms the monoclonal, larger antibody delivers radiation to cancer cells for longer. Telix are trialling 2x 76mCi doses whilst Pluvicto is ~6x 200mCi. Antibodies circulate more radiation for longer and the organ risk profile shifts to bone marrow from salivary/kidney. The trade off is essentially a bigger radiation punch vs higher toxicity. This is where I disagree and think Pluvicto is operating at the front of the optimal curve of radiation/safety relative to TLX591. For this drug to be approved it would either need to show equal or greater efficacy to Pluvicto or offer a clinical advantage Pluvicto can’t - likely some advantage being used in tandem with ARPI or docetaxel.
History of TLX591 (177Lu-rosopatamab)
1a) Huj591 was developed by Dr Neil Bander (via his firm BZL biologics) In 2001 Takeda licensed the drug to carry out trials testing dose limiting toxicity and PSA (prostate cancer protein) decline. The trial failed it’s primary endpoint of >50% PSA decline and noted high neurotoxicity rates.
The drug was returned to returned back to BZL/Bander.
1b) The drug sat dormant till 2009 when it was licensed to a new firm, Atlab Pharma to conduct Ph1 trials that trialled the combined the effect of docetaxel + Huj591, primary endpoint being dose limiting toxicity. It passed primary endpoint at max dose 2x40mCi (n=5). Note the current ph3 trials are 2x76mCi dosages so there is not much signal to Telix here.
The trial took 6 years from finishing in 2015. Safe to say no one was in a rush here.
It’s not abundantly clear who became involved when. Telix claim in their prospectus that Huj591 was licensed to Atlab Pharma 2011 but the trial started in 2009.
The peer reviwed mentions Telix as a sponsor which is strange considering Telix were not incorporated until 2017. This trial started in 2009 and finished primary completion in 2015.
It’s possible they jumped in late and threw some money at getting the trial peer reviwed, but were not involved in the trial itself.
https://clinicaltrials.gov/study/NCT00916123?intr=monoclonal%20antibody%20J591&rank=6#study-plan
https://www.sciencedirect.com/science/article/abs/pii/S1078143920302593?fr=RR-2&ref=pdf_download&rr=9715f137494080f2
1c) 2013 we move forward to a Ph2 trial led by Neil Bander and Atlab Pharma. Primary endpoint was >50% decline in PSA (n=47). The trial failed with primary endpoint p=1.00, literally the worst statistical score possible. A second endpoint was added during after the trial had begun of >30% PSA decline. It passed, barely p=0.048. The higher dosage was 70mCi/m^2 - BSA (body surface area) dosage. This is notable given under Telix’ reign, the 591 trials ditched BSA trialling.
The toxicology result in 70mCi/M^2 was …. bad. 46% had grade 4 had SAE (serious adverse events).
1d) 2023. Telix engages ph1 ProstACT Select trials (n=30) testing primary endpoint; dose limiting toxicity. This trial was to collect safety/dosimetry data, which the FDA had recommended.
The trial passed its primary endpoint however it took 20 months vs. guided 12 months and only had n=30 enrollment vs planned n=50. Again, no explanations here.
The results from this trial are ‘fine’ in my opinon, but I question the trial design.
Novartis PSMAfore trial (n=470) is not like for like by any means but analysis between there are clear differences in the patient inclusion criteria. The bar is higher for 591; Select requires 150x109L platelets (bone marrow cells), 50% higher than PSMAfore. Hemoglobin criteria is also higher. In english… Telix require patients with healhier bone marrow.
At this stage it’s worth highlighting that Telix have pivoted from the body surface area dosage to flat dosing. Theoretically (I’m not asserting Telix have done this) you can use ‘larger’ subjects to subterfuge results.
A critic would argue that PSMAfore is not the same and these differences are meaningless, sure.
But when it came to announcing interim readouts, Telix disclosed this: “Serious adverse events (SAEs) observed were generally lower than in earlier studies conducted at the same dose level, reflective of the SELECT study being conducted in a healthier patient population”
July 2025. Telix have since been hit with a SEC subpoena relating to “the Company’s disclosures” for prostate therapies ala TLX591.
ProstACT Select trials were finished Sep 2023 - we have had 2x interim readouts insofar. 23 months later we have not seen the full results or had a peer published study.
Strange - every other trial I’ve referred to here has a peer reviwed paper available online. Why does Select not?
1e) The big dawg; ProstACT Global ph3 RCT trialling Lu177+SoC vs. SoC only (2:1), Primary endpoint rPFS. Very broad control arm where SoC can be hormonal therapies or chemo.
Telix had publicly guided to 1H25 part readouts for this trial. They quietly walked this back at 2Q25 without explanation.
Not a single sellside analyst wrote about the guidance withdrawal which is fucking amazing given it its’ outcome is the material driver of the stock NTM.
It took them ~12 months to consent n=30 patients to the trial which is a whopping 2.5 patients/month enrollment rate.
Again, no queries here from the street.
Disclaimer:
This is a blog of my thoughts of some securities. It is not financial advice.
The information contained in this post is for informational and entertainment purposes only and should not be construed as financial, investment, or other professional advice. I may hold or trade positions in the securities discussed, and such positions may change at any time without notice. All opinions expressed are solely my own, based on publicly available information, and do not constitute a recommendation to buy, sell, or hold any security.