Porter’s First Biotech Recommendation Up 40%

If there was one thing I could do for every single subscriber, I would give you the ability to understand what’s happening right now in biotechnology (aka, novel drug development).

My first recommendation in Porter & Co Biotechnology was up almost 40% this morning on huge volume. I told our subscribers exactly why this would happen 10 days ago. And today I want to tell all of you the entire story, whether you’re a Partner yet at Porter & Co or not.

I mean it when I say:

If there was one thing I could do for every subscriber, it’s to give you the ability to understand what’s happening right now in biotechnology.

All you have to do is give me 10 minutes.

But I know, for virtually all of you, this is a bridge way, way too far. There is so much jargon and so many unknowns in biology. There is so much risk.

All true. But it is changing. Over the last 20 years, our understanding of human biology has improved by several orders of magnitude. There’s one new, well-proven modality in particular that will deliver trillions in profits for investors. And I’m 100% certain you can understand it.

It’s gene silencing. Its chemistry and mechanism of action were discovered in the late 1990s and billions have been spent on development since. It is now well proven. It’s not hard to understand either. Where the body is malfunctioning, this approach interrupts the cellular mechanisms causing disease: it stops the malfunction at its source. This has the promise of new cures and vastly better cures.

The difficulty in this new approach, for more than 20 years, has been delivering the drug to inside the cells, where it “silences” disease by interfering with RNA. Because these drugs must be delivered inside the cell, the delivery technology must be developed and proven for every type of tissue, which means the developmental timeline for this class of medicine will be decades.

The good news: Delivery to inside liver cells has been cracked and, for the first time ever, gene-silencing medicines are now generating billions in revenue.

I call gene silencing my “Fourth Kingdom” (out of 11) of drug development. Silence Therapeutics (SLN) is one of four gene-silencing companies I recommended to subscribers in the August Porter & Co. Biotechnology. This morning Silence delivered top-line data on its Phase II clinical trial ("SANRECO"), for the developmental drug divesiran, which treats a rare blood cancer, polycythemia vera (“PV”).

SLN is now trading around $16, up 38% on 12.8× average volume. As we wrote in our launch issue earlier this month, we believe gene silencing (using RNA interference) will become the next major modality across biotech and will emerge, much as fully human monoclonal antibodies did in the 2010s, as one of the best investments in the world.

For those new to our work, RNA interference is a natural cellular process – discovered in worms – where short pieces of double-stranded RNA (siRNA) latch onto a specific messenger-RNA (mRNA) and tell the cell to shred it before it can be translated into a protein. If you can pick which mRNA to destroy, you can turn off any disease-causing gene in the body. This approach has been proven commercially by Alnylam Pharmaceuticals (ALNY) with drugs like Amvuttra. Silence Therapeutics owns its own independent siRNA chemistry patents (mRNAi GOLD), which gave it a legal path to develop liver-targeted siRNAs while avoiding Alnylam's patents.

PV is a rare blood cancer where the marrow makes too many red cells. Today's treatment is repeated phlebotomies (bleeding patients like it's 1780). Divesiran restricts the iron supply the marrow needs – starving the disease of its raw material. Phase I essentially eliminated phlebotomies.

But Phase II was the real test. Silence enrolled 48 patients, all of them dependent on regular phlebotomy, and randomly assigned them to receive divesiran or a placebo in a double-blinded trial. Divesiran was given as a 6 milligram injection under the skin, on one of two schedules: every six weeks or every 12 weeks. The measure of success was harsh. To count as a responder, a patient had to keep their hematocrit (the concentration of red cells in the blood) under 45% and require zero rescue phlebotomies. One bleed and the patient was out.

Divesiran cleared the bar – strongly… 88% of divesiran patients responded, against 19% on placebo. And both dosing schedules worked. The every-six-week arm produced a 93.8% response rate. The every-12-week arm produced 81.3%. A drug that only requires four injections a year that’s delivering better than eight out of 10 patients into full disease control, will become a strong chronic-therapy franchise.

Patient-reported symptom scores on the MPN-SAF scale improved, meaning patients actually felt better, not only that their labs looked better. Safety was clean.

Silence now plans to start a Phase III trial in PV, testing the every-12-week schedule against placebo, in the first half of 2027.

But that’s not what matters. This is only the first step toward developing what will become the best-selling drug in history.

SANRECO proved that Silence's platform can durably and safely silence a human liver gene, with a dosing schedule as long as 12 weeks between injections, in a randomized, placebo-controlled, blinded trial. Divesiran silences a gene called TMPRSS6 in the bone marrow's iron supply chain. While that’s critical to people with PV, for investors there are much, much more valuable liver genes to silence.

Zerlasiran, Silence's next drug, silences Lipoprotein(a) – Lp(a) – which is a liver gene that makes a nasty variant of LDL cholesterol that’s believed to be a major risk factor for cardiac events. Your Lp(a) levels are set almost entirely by the LPA gene you inherit from your parents. Diet doesn't move it. Exercise doesn't move it. Statins don't move it. Roughly one in five people worldwide, about 1.5 billion of us, are born with high Lp(a), and high Lp(a) is one of the strongest independent genetic risk factors known for heart attack, stroke, and aortic valve disease.

Until now, there has been no approved drug that lowers it. That is why every large pharmaceutical company with a cardiovascular franchise – Novartis (NVS), Amgen (AMGN), Eli Lilly (LLY), Merck (MRK) – is either running or funding an Lp(a)-lowering trial right now.

Zerlasiran is Silence's shot at that prize. It uses the same siRNA chemistry SANRECO just validated, delivered by the same liver-targeting sugar tag, on the same infrequent dosing schedule that Silence's Phase II data now proves works in humans.

The first of this new class of Lp(a) targeting drugs will report pivotal Phase III data this fall and could be on the market as soon as 2028. Our subscribers know who owns it and how to invest in it. I hope all of you will join us.

Silence has now proven that its chemistry can deliver safe, durable gene silencing at a commercially viable dosing schedule. That means it’s now in the race for what will likely be a best-selling class of drugs for the next two decades.

To see what Porter has to say next in Porter & Co. Biotechnology, click here.

Tell me what you think of today’s Daily Journal: porterstansberrydirect@gmail.com

Good investing,

F. Porter Stansberry
Stevenson, Maryland