Since we are talking about potential competition, let me riff off on Immutep and "efti" one final time. The comparison with Cytodyn is especially relevant because they share so many similarities--it's like the companies are corporate doppelgangers on opposite sides of the Pacific (IMM is listed on the Aussie market and headquartered in Sydney; their ARDs are listed on NASDAQ as IMMP). There is a Merck connection here that I'm sure the board will be interested in... which I'll save for last.
Both biotechs are penny stock companies that get relentlessly shorted and manipulated, yet persist with cutting-edge science. Immutep is currently 38 Aussie cents a sharewith a market-cap of 388 million USD. IMMP is something like $2.72 a share here in the US.
Both LL and efti are subcutaneous injectables that are extremely safe and can be administered to existing SOC cancer therapies (chemo and other IO drugs). In one breast cancer trial, efti outperformed placebo in terms of side effects, as did LL in the mild-covid trial.
Like LL compared to maraviroc and other CCR5 inhibitors, efti was designed extremely well. Dr. Frederic Triebel, who is still with the company, discovered Lymphocyte Activation Gene-3 in 1990. He went on to create a soluble LAG-3 fusion protein, as an APC activator that binds to Major Histocompatibity Complex II (MHC-II) on dendritic cells and monocytes. As an APC activator, efti is a superior drug compared to the LAG-3 inhibitors Merck and other firms developed to treat cancer (though relatlimab (BMS) does work reasonably well paired with Opdivo in melanoma).
Immutep's has another LAG-3 candidate, IMP761, for autoimmune diseases, much like LL has great potential as a broad-spectrum anti-inflammatory. (See Ohm's List).
Let's talk data in first-line NSCLC. Efti is paired with Keytruda and chemo in the Insight-003 trial, 51 patients, stratified by low, medium, and high PD-L1 status:
TPS<1%-- 54% ORR (Keytruda/chemo--32%)
TPS 1-49%--68% ORR (Keytruda/chemo--49%)
TPS>50%--75% ORR. (Keytruda/chemo--62%)
PFS--12.7 months (vs 9 m Keytruda/chemo)
OS--32.9 months. (vs 22m Keytruda/chemo)
Pretty solid numbers. Not 5 outta 5 (mTNBC)... closer to 3 outta 5 (mCRC). But clearly, efti primes patients with low and medium PD-L/PD-L1 expression to do significantly better with an ICI. Immutep did another Phase II trial (TACTI-002) with 114 patients, without chemo. Not as good as with, but still much better than Keytruda as a monotherapy, especially in low and medium PD-L1 expression. They also have done other trials in Head and Neck carcinomas, breast cancer and sarcomas--and efti has done well, beating the standard of care in all those trials (except breast cancer) with no new safety issues. And similar to Cytodyn, at least a couple of these trials were investigator-initiated, so there is clearly an interest in the drug among the medical community. They are currently in Phase III registrational trial (TACTI-004), with over half of their expected 750 patients enrolled and on the drugs. With a futility review is expected to be completed by their DSMB end of Q1.
The Merck connection/conundrum:
On the Immutep website they refer to Merck as a "partner." So, what kind of deal did they get from Merck for a potentially Best-In-Class drug that would extend Keytruda's patent protection for many years in first-line NSCLC? They got free Keytruda for the trials. (!) No upfront money, no milestone payments. Co-development and marketing rights, if I recall correctly. If you think Cytodyn investors are drooling over a potential Merck partnership or buyout... well, Immutep investors are scratching their heads... and I'm going bat-shit crazy. Compared to Cytodyn, Immutep has a much larger data set in it's favor, with significantly more clinical trials in four different cancers. And the first-line NSCLC market, which efti addresses irrespective of PD-L1 status, is huge. So what gives?
I kid you not--Immutep got more in a deal with Dr Reddys than from Merck. Dr Reddy's! They are developing a generic Keytruda that they plan to pair with efti in ex US/Europe/Japan/China. Something like 20 million dollars upfront, $300 million or so in milestones, and double-digit royalties. I thought it was a clever move by Immutep, put a little pressure on Merck, maybe?
Well, as Cytodyn investors, what can we learn from all this? That Merck is a cheap-ass potential partner? Perhaps... But there is a futility analysis for the Phase III trial that is due soon, by the end of Q1. So maybe Merck is waiting on that. I could see a risk-averse, corporate heavyweight like Merck being cautious, playing hardball, much like Jake has suggested how these things go. But are they really going to play a game of chicken like this, waiting on the futility analysis, when another Big Pharma with an ICI could come along and partner or snatch them from right under their nose? Man, if Merck is playing that game, they have some big stones...
Watching this saga play out has definitely affected how I see Merck as a potential partner. And that is not even talking about how much money they have thrown at other cancer therapeutics, which I have discussed in other posts. And there is this--like Merck's earlier tests with the CCR5 inhibitor vicriviroc back in 2019-21, they have experience with a LAG-3 inhibitor, favezelimab, that failed earlier cancer trials. Perhaps they are a little gun-shy about both CCR5 and LAG-3 inhibitors. Maybe they think the mRNA boost to Keytruda's effectiveness is enough to keep them competitive in most of the indications Keytruda is already approved for, even if LL works as advertised in mCRC and mTNBC. Maybe they are getting an NDA ready for the CCR5 asset they received in the Cidara buyout, as another option?
So, if Merck is so smart, why didn't they make a play for both Cytodyn and Immutep back in 2023... or earlier? They certainly would have gotten both on the cheap, or cheaper, and kept the cash they forked over for all the other cancer assets they have recently acquired. I will be carefully watching what Merck does after the futility analysis with efti. If they buyout Immutep I would think Merck is a big negatory on a deal with Cytodyn. If they don't I would think they are crazy... but it would keep the door open, a bit, for a deal with Cytodyn. I still don't think they will based on previous commitments, institutional inertia and hubris... but who knows?
One final thought--Why not test efti and leronlimab together against cancer? Pre-clinical work, anyway. The best-in-class LAG-3 antigen-presenting cell activator paired with the best-in-class CCR5 inhibitor. Kat thought the idea was interesting, anyway... Maybe the combination would bump the PD-L1 percentage from 88% closer to a big fat 100%, and let an ICI do the rest. Or the combo might work better as a first-line treatment and save the ICI for second line, with or without chemo. One thing I am confident in--both drugs have a great future as cancer therapeutics, and both are going places soon.
If you are reading this you probably know a lot about leronlimab. Here's a link to the latest Corporate Presentation from Immutep if you are curious about efti. Oh, I should probably say--this is all speculative, and shouldn't be considered either medical or financial advice. And sorry for the long post... though I don't feel bad for trying to be thorough...
https://www.immutep.com/dw/uploads/2026/02/Im...eb2026.pdf
Both biotechs are penny stock companies that get relentlessly shorted and manipulated, yet persist with cutting-edge science. Immutep is currently 38 Aussie cents a sharewith a market-cap of 388 million USD. IMMP is something like $2.72 a share here in the US.
Both LL and efti are subcutaneous injectables that are extremely safe and can be administered to existing SOC cancer therapies (chemo and other IO drugs). In one breast cancer trial, efti outperformed placebo in terms of side effects, as did LL in the mild-covid trial.
Like LL compared to maraviroc and other CCR5 inhibitors, efti was designed extremely well. Dr. Frederic Triebel, who is still with the company, discovered Lymphocyte Activation Gene-3 in 1990. He went on to create a soluble LAG-3 fusion protein, as an APC activator that binds to Major Histocompatibity Complex II (MHC-II) on dendritic cells and monocytes. As an APC activator, efti is a superior drug compared to the LAG-3 inhibitors Merck and other firms developed to treat cancer (though relatlimab (BMS) does work reasonably well paired with Opdivo in melanoma).
Immutep's has another LAG-3 candidate, IMP761, for autoimmune diseases, much like LL has great potential as a broad-spectrum anti-inflammatory. (See Ohm's List).
Let's talk data in first-line NSCLC. Efti is paired with Keytruda and chemo in the Insight-003 trial, 51 patients, stratified by low, medium, and high PD-L1 status:
TPS<1%-- 54% ORR (Keytruda/chemo--32%)
TPS 1-49%--68% ORR (Keytruda/chemo--49%)
TPS>50%--75% ORR. (Keytruda/chemo--62%)
PFS--12.7 months (vs 9 m Keytruda/chemo)
OS--32.9 months. (vs 22m Keytruda/chemo)
Pretty solid numbers. Not 5 outta 5 (mTNBC)... closer to 3 outta 5 (mCRC). But clearly, efti primes patients with low and medium PD-L/PD-L1 expression to do significantly better with an ICI. Immutep did another Phase II trial (TACTI-002) with 114 patients, without chemo. Not as good as with, but still much better than Keytruda as a monotherapy, especially in low and medium PD-L1 expression. They also have done other trials in Head and Neck carcinomas, breast cancer and sarcomas--and efti has done well, beating the standard of care in all those trials (except breast cancer) with no new safety issues. And similar to Cytodyn, at least a couple of these trials were investigator-initiated, so there is clearly an interest in the drug among the medical community. They are currently in Phase III registrational trial (TACTI-004), with over half of their expected 750 patients enrolled and on the drugs. With a futility review is expected to be completed by their DSMB end of Q1.
The Merck connection/conundrum:
On the Immutep website they refer to Merck as a "partner." So, what kind of deal did they get from Merck for a potentially Best-In-Class drug that would extend Keytruda's patent protection for many years in first-line NSCLC? They got free Keytruda for the trials. (!) No upfront money, no milestone payments. Co-development and marketing rights, if I recall correctly. If you think Cytodyn investors are drooling over a potential Merck partnership or buyout... well, Immutep investors are scratching their heads... and I'm going bat-shit crazy. Compared to Cytodyn, Immutep has a much larger data set in it's favor, with significantly more clinical trials in four different cancers. And the first-line NSCLC market, which efti addresses irrespective of PD-L1 status, is huge. So what gives?
I kid you not--Immutep got more in a deal with Dr Reddys than from Merck. Dr Reddy's! They are developing a generic Keytruda that they plan to pair with efti in ex US/Europe/Japan/China. Something like 20 million dollars upfront, $300 million or so in milestones, and double-digit royalties. I thought it was a clever move by Immutep, put a little pressure on Merck, maybe?
Well, as Cytodyn investors, what can we learn from all this? That Merck is a cheap-ass potential partner? Perhaps... But there is a futility analysis for the Phase III trial that is due soon, by the end of Q1. So maybe Merck is waiting on that. I could see a risk-averse, corporate heavyweight like Merck being cautious, playing hardball, much like Jake has suggested how these things go. But are they really going to play a game of chicken like this, waiting on the futility analysis, when another Big Pharma with an ICI could come along and partner or snatch them from right under their nose? Man, if Merck is playing that game, they have some big stones...
Watching this saga play out has definitely affected how I see Merck as a potential partner. And that is not even talking about how much money they have thrown at other cancer therapeutics, which I have discussed in other posts. And there is this--like Merck's earlier tests with the CCR5 inhibitor vicriviroc back in 2019-21, they have experience with a LAG-3 inhibitor, favezelimab, that failed earlier cancer trials. Perhaps they are a little gun-shy about both CCR5 and LAG-3 inhibitors. Maybe they think the mRNA boost to Keytruda's effectiveness is enough to keep them competitive in most of the indications Keytruda is already approved for, even if LL works as advertised in mCRC and mTNBC. Maybe they are getting an NDA ready for the CCR5 asset they received in the Cidara buyout, as another option?
So, if Merck is so smart, why didn't they make a play for both Cytodyn and Immutep back in 2023... or earlier? They certainly would have gotten both on the cheap, or cheaper, and kept the cash they forked over for all the other cancer assets they have recently acquired. I will be carefully watching what Merck does after the futility analysis with efti. If they buyout Immutep I would think Merck is a big negatory on a deal with Cytodyn. If they don't I would think they are crazy... but it would keep the door open, a bit, for a deal with Cytodyn. I still don't think they will based on previous commitments, institutional inertia and hubris... but who knows?
One final thought--Why not test efti and leronlimab together against cancer? Pre-clinical work, anyway. The best-in-class LAG-3 antigen-presenting cell activator paired with the best-in-class CCR5 inhibitor. Kat thought the idea was interesting, anyway... Maybe the combination would bump the PD-L1 percentage from 88% closer to a big fat 100%, and let an ICI do the rest. Or the combo might work better as a first-line treatment and save the ICI for second line, with or without chemo. One thing I am confident in--both drugs have a great future as cancer therapeutics, and both are going places soon.
If you are reading this you probably know a lot about leronlimab. Here's a link to the latest Corporate Presentation from Immutep if you are curious about efti. Oh, I should probably say--this is all speculative, and shouldn't be considered either medical or financial advice. And sorry for the long post... though I don't feel bad for trying to be thorough...
https://www.immutep.com/dw/uploads/2026/02/Im...eb2026.pdf
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