[Editors Note – The following is a guest post that originally appeared almost a year ago. It is about everyone’s favorite reverse-merger pink sheet Coronacrapper-turning-Cancercon, Cytodyn (CYDY) from @B4UConsent, a real life patient with tremendous insight into drug development from both the patient and the clinical trial management perspectives. Given this morning’s nonsensical press release from Cytodyn, it is timely to re-up her thoughts.]

BuyersStrike has generously invited me – patient, investor, blogger at B4UConsent – back to do a guest post on CytoDyn’s TNBC delusions. Happy to help!

Today we sink from the height of scientific rigor and strategic foresight we witnessed with Roche’s IMpassion program to the sewage ditch that is CytoDyn’s attempt to take on – wait for it – triple-negative breast cancer (TNBC). TNBC is, for the uninitiated, the rarest breast cancer subtype, exhibiting no hormone receptors nor overexpressing the HER2 protein, which make patients ineligible for anti-hormonal agents or HER2-targeted agents. Further, this tends to be an aggressive subtype that occurs in younger patients, and it’s associated with the poorest outcomes.

Historically, while TNBC patients have had few treatment options beyond chemo, there have been advances, particularly with immunotherapy. Roche received an accelerated approval for the combination of atezolizumab plus the chemo drug Abraxane, to be used in the first line. Sacituzumab govitecan, from Immunomedics (IMMU) more recently received accelerated approval in third line. Atezo/Abraxane is the standout here, and I have my reservations about sac gov, but there’s no disputing that these accelerated approvals were hard-won on PFS (progression free survival) data. Roche and Immunomedics are now just left to sweat out the wait on those OS (overall survival) numbers.

In contrast, CytoDyn got rid of a fake tumor engrafted on a mouse that one time.

And since in the fever dreams of its retail fanbase, and delusional (at best) management team, leronlimab has already “cured” COVID and HIV, with GvHD and NASH (and MS and Alzheimers, and on and on and on) on deck, why not throw TNBC in the mix? It’s not like it’s hard to design, recruit and run a cancer trial. CytoDyn is generously “keep[ing] the FDA current” on their miracle outcomes, which seem largely limited to meaningless, outdated lab markers (CTCs, really?) and not the more meaningful outcomes we in cancer are all familiar with, things like, “Tumor in lung got 31% smaller.” I’m sure our friends at the Agency are eagerly anticipating these updates and sending them straight to voicemail.

The most telling press release about the garbage this company is peddling is from January 13.

They reference two patients, one of whom is apparently enrolled in the company’s phase 1b/2 study which enrolls previously untreated metastatic breast cancer patients. You can tell a patient to drink more water in the first-line setting and get at least a modest response, which is why it should be a GCP violation to enroll subjects first-line for completely unproven drugs. You get one shot at first-line, one chance to maximize response and the duration of response. We know response rates get lower with each line of treatment.

In this case, the company felt compelled to announce that their first TNBC subject had a reduction in circulating tumor cells (CTCs). This is a) not an endpoint and b) not clinically relevant. No one does CTC tests, and they were never adopted widely because they were useless. They were never sensitive enough; you could be a walking tumor and have a CTC of 0. Plenty of metastatic patients have CTCs of 0, and a CTC result higher than 5 would signal full-on death watch. A more modern and useful marker would be ctDNA, which are small fragments of tumor that are used in the liquid biopsy tests we have from Guardant and Foundation Medicine.

Guess what else? “This patient’s data also demonstrated tumor shrinkage of >20% after just a few weeks of treatment.” Greater than 20%, that sounds good, right? It’s actually not. It means the disease has remained stable. In cancer, we use one guideline to interpret tumor size and response on scans: it’s called RECIST 1.1, and the rules are very clear. As a former medical writer on oncology trials, I can recite them in my sleep: a complete disappearance of disease is a Complete Response, or CR; reduction in disease >25% is a partial response, or PR; change in tumor measurement <25% but not increasing in size by more than 25% is defined as stable disease, which is NOT considered a response; and increase in tumor measurements by >25% is progressive disease, or PD.

So by the accepted laws of oncology, this patient is an SD. The CTCs are meaningless.

And what of the second patient?

She was not enrolled in a trial. She received treatment under an “emergency IND protocol” and is described as having “HER2+ metastatic, stage 4, MBC” and “showed no sign of new metastatic spots in the liver, lung and brain during the treatment with leronlimab.” Yeah, no new lesions is always nice, but what about the lesions she had at baseline? Subsequent press releases also suggest that this patient was receiving other treatment concurrently, so how could we attribute anything positive to the leronlimab?

This nonsense concludes with, “This strong data confirms the power of leronlimab as a CCR5 inhibitor for patients living with mTNBC, and is clearly replicating early animal study results that demonstrated 98% elimination of metastases.” (Emphasis mine.)

What’s that, now? That little mouse had what would probably be classed as a CR. These two patients didn’t even respond.

But why stop at TNBC when the data are so compelling? That’s a tiny little sliver of the cancer population. Aren’t there a lot more cancers to cure and patients, shareholders and innocent bystanders to manipulate?

That brings us to the basket trial, open to all solid tumors, which seems to have just started enrolling a few days ago. “All solid tumors” will apparently be represented in a 30-subject phase 2 at one site, something called “Quest Clinical Research” in San Francisco. Just the name evokes the echelons of scientific development, no?

Let’s review the primary endpoints for this “trial” together, shall we?

1. Number, frequency, and severity of adverse events (AEs)
2. Incidence of abnormal laboratory tests results
3. Changes in Eastern Cooperative Oncology Group (ECOG) performance status from baseline to subsequent scheduled visits

Are 1 and 2 not the same? And … what is 3 supposed to demonstrate? That is not an endpoint for approval in oncology. The enrollment criteria specify an ECOG status of 0-1 (that’s fully active to slightly less active; by 2, patients are getting pretty debilitated). So we’re looking at a phase 2 with no PFS endpoint. This study is exposed as even more of a sham by a line in the study description section:

Subjects participating in this study will be allowed to receive/continue standard-of-care chemotherapy or radotherapy [sic] as per the dosing schedule included on the package insert.

Let me get this straight. Subjects have the option of staying on therapies that are already working and just adding an experimental agent. What exactly is being tested here? Who would enroll in something like this, and why would anyone let them? Are they trying to design a “study” that can’t fail by deliberately rejecting the efficacy and enrollment standards by which a whole industry abides?

Though we don’t have answers, we do have a lesson: stay away from this bioturd. At least the mouse made it out.

Thanks again to BuyersStrike for having me.

THE CONTENT CONTAINED IN THIS BLOG REPRESENTS ONLY THE OPINIONS OF THE AUTHOR. THE AUTHOR MAY HOLD EITHER LONG OR SHORT POSITIONS IN SECURITIES OF VARIOUS COMPANIES DISCUSSED IN THE BLOG. THIS COMMENTARY IN NO WAY CONSTITUTES INVESTMENT ADVICE, AND SHOULD NEVER BE RELIED ON IN MAKING AN INVESTMENT DECISION, EVER. THIS BLOG IS NOT A SOLICITATION OF BUSINESS: ALL INQUIRIES WILL BE IGNORED. THE CONTENT HEREIN IS INTENDED SOLELY FOR THE ENTERTAINMENT OF THE READER, AND THE AUTHOR.

Today is one of those special days in the saga of everyone’s favorite reverse-merger pink sheet Coronacrapper, Cytodyn (CYDY). A day where The NaDDir* issued not one, not two, but three, ridiculous press releases seemingly devoid of substance.

But only seemingly.

Compare the boilerplate about Cytodyn’s ill-fated BLA re-submission for loserlimab in HIV from last week:

to the new boilerplate from today’s nonsense:

Oops. There it is, the one little bit of real information they tried to bury under a pile of bullshit. That pivot to a ridiculous cancer cure cannot come soon enough for the Klown Krew.

* Spelled Thusly For A Double Dose of That Sweet Sweet Stock Pimping

THE CONTENT CONTAINED IN THIS BLOG REPRESENTS ONLY THE OPINIONS OF THE AUTHOR. THE AUTHOR MAY HOLD EITHER LONG OR SHORT POSITIONS IN SECURITIES OF VARIOUS COMPANIES DISCUSSED IN THE BLOG. THIS COMMENTARY IN NO WAY CONSTITUTES INVESTMENT ADVICE, AND SHOULD NEVER BE RELIED ON IN MAKING AN INVESTMENT DECISION, EVER. THIS BLOG IS NOT A SOLICITATION OF BUSINESS: ALL INQUIRIES WILL BE IGNORED. THE CONTENT HEREIN IS INTENDED SOLELY FOR THE ENTERTAINMENT OF THE READER, AND THE AUTHOR.

We have reached a repeat moment in the saga of everyone’s favorite reverse-merger pink sheet Coronacrapper, Cytodyn (CYDY). The time when, after a study failure, the criminal stock promoters, various shills, and the retail shareholder base of complete morons suddenly become “experts” in “teh science”, results be damned. [Catch up on Part 1 of But Teh Science Be So Gud, from August 2020, here.]

After three morning press releases and then last afternoon’s delusional CONference call rantings from The NaDDir*, and his Klown Krew, yesterday the company issued an 8k with some (and only some) actual data from the failed CD12 study of leronlimab (lovingly referred to as loserlimab at BuyersStrike! HQ). The filing is available here.

The document is almost more noteworthy for what it doesn’t include, rather than the various post-hoc data dredged subgroups that it does include. Nowhere does it actually answer the question, “Does loserlimab actually save lives versus placebo?” Not mixed with a variety of other drugs, not when mixed with a variety of other drugs and dexamethasone, but does it actually do anything head to head against placebo? In order to answer that question one of our overworked interns volunteered to back out the numbers from the scant data that was provided.

Table 1-1 provides some mortality data overall for the mITT population. “mITT” is jargon for “modified intent-to-treat” and typically mITT is frowned upon, especially when the data from the ITT (without modification) population is not given. Nevertheless, it is all we have from the company. From this we learn that there were 259 patients in the loserlimab arm and 125 in the placebo arm. There were 53 deaths in the loserlimab arm (20.5% mortality), and 27 in the placebo arm (21.6% mortality). Although not given by Cytodyn, the difference is nowhere near statistically significant, the p-value is a whopping 0.79.

Many of these patients were taking all sorts of other therapies, and The NaDDir* is especially proud of one particular post-hoc subgroup analysis, patients who were on other prior or concomitant treatments:

The given p-value is actually suspect as the company admits “Note: p-value is from logistic model adjusted for stratification factor and age based on non-missing observed data.” A more standard calculation of the p-value would yield p=.167, which is still crap, but at least not p=.79 crap. Behold the power of post-hoc data mining.

But this chart still doesn’t tell us anything about the effects of loserlimab alone versus placebo alone. How did patients who were only taking loserlimab do versus those only taking placebo? Does leronlimab really save lives? Cytodyn does not provide the answer. But we will.

In order to answer that question, one needs to back out the 309 subjects above, those who took other treatments, from the 384 total subjects in the trial. Then we need to back out the 58 deaths in that group from the 80 deaths overall. That gives us 75 subjects (21 placebo, 54 loserlimab) and 22 deaths (3 placebo and 19 loserlimab). Plug those numbers into Excel, and presto, the answer to the question, “Does loserlimab actually save any lives?” is a resounding “NO.”:

35% of subjects receiving loserlimab alone died compared to only 14% of controls. The p-value happens to be 0.075, results that, as The NaDDir* would say are “Very Exciting!” and “Approaching Statistical Significance!” So much for “saving teh livez” with “teh science that be so gud!”

* Spelled Thusly For A Double Dose of That Sweet Sweet Stock Pimping

THE CONTENT CONTAINED IN THIS BLOG REPRESENTS ONLY THE OPINIONS OF THE AUTHOR. THE AUTHOR MAY HOLD EITHER LONG OR SHORT POSITIONS IN SECURITIES OF VARIOUS COMPANIES DISCUSSED IN THE BLOG. THIS COMMENTARY IN NO WAY CONSTITUTES INVESTMENT ADVICE, AND SHOULD NEVER BE RELIED ON IN MAKING AN INVESTMENT DECISION, EVER. THIS BLOG IS NOT A SOLICITATION OF BUSINESS: ALL INQUIRIES WILL BE IGNORED. THE CONTENT HEREIN IS INTENDED SOLELY FOR THE ENTERTAINMENT OF THE READER, AND THE AUTHOR.

We continue to wait for The NaDDir*, and his klown krew, at everyone’s favorite reverse-merger pink sheet Coronacrapper, Cytodyn (CYDY) to actually reveal the top line results from the CD12 study of loserlimab for Severe-to-Critical Chinese Coronavirus Disease. With all of this extra time, we will continue our look back at Cytodyn’s long history of broken, empty, promises. Failing to deliver is a bit of a specialty for the klown krew.

Many readers are aware of Cytodyn’s laughable promises of using their drug as a monotherapy for HIV treatment. Why laughable? Because even if you take the company at its word (we don’t), loserlimab only blocks one strain of HIV (there are two strains). This is why the existing, approved, drug on the market, maraviroc, which does exactly what Cytodyn’s drug does, is not used for monotherapy. There are other drugs already on the market, like Trogarzo, that block both strains. And there are other drugs further ahead in development from Viiv and others, including a once-every-six-month subcutaneous treatment, from Gilead (GILD). Read more about those here.

For over four years Cytodyn has been running its Phase 3 HIV monotherapy trial, often referred to as CD03. Details can be found here. The trial started in August 2016, although the company has been eerily silent about it for a little over two years.

For quite some time, Cytodyn press releases carried a little bit of boilerplate about the trial at the bottom. Here is an example from the 2nd of Sept 2020:

Just a few weeks later, on the 20th of September, the boilerplate changed:

Sometime in mid-September 2020, the CD03 trial has been completed. Yet five months later there is still no press release announcing results, no 8k has been filed with the SEC, and the klown krew could not even update Clinicaltrials.gov records. Seems strange for a Phase 3 trial of a supposedly revolutionary treatment. The only clues we have about how the trial had been faring are from an interim look at the data. The company issued a press release in November 2018 stating:

Unlike 2020’s CROI debacle, which we looked at a few days ago, this time the poster actually was available at the conference. You can look it up here, and download the poster for yourself here. What you will find is, well, not good. The interim look at CD03 caught all of the patients in the 350mg dose group (which is actually 2 injections of 175mg each), the 525mg group (3 injections x 175mg) and only some of the 700mg dose group (yes…even more injections!). While The NaDDir* loves to mention the handful of patients that have done well on conference calls, does he ever mention the huge numbers of patients that failed on loserlimab monotherapy? See the boxes entitled Virologic Failure. Here is a hint for biotech neophytes, failure is bad:

Well even though monotherapy is singularly unimpressive, at least they have that safety record to tout, right? It is true that injection site reactions appear to be uncommon. The same cannot be said about other Adverse Events (AEs).

Anywhere from 48% to 75% of subjects experienced at least one AE. Somewhere between 3.5% and 8.4% of patients experienced a Serious Adverse Event (SAE). One might notice the Cytodyn never reveals exactly what these AEs are, nor their grade. The bulls might say, “oh, but the company says ‘None of the reported SAEs were definitely or probably related to PRO 140.’ that means it is safe.” According to whom? The company? The company’s hired gun CRO? The investigators who may have tremendous conflicts? What of the possibly related SAEs and the unlikely but possible ones?

Of course the easiest way to know the CD03 trial failed is just to look at the boilerplate of recent Cytodyn press releases, like the one from earlier this week. Notice what the company says about the CD02 trial versus the CD03 trial (and the CD10 trial for good measure). Here’s CD02:

And CD03:

And for fun, CD10:

What a difference that one little word in the boilerplate makes. The late 2019 pivot to cancer, and the 2020 pivot to Chinese Coronavirus Disease makes all the more sense. Will we ever see the real, complete, CD03 results? Will we ever see the real, complete, CD10 results? And will we ever see the real, complete CD12 results? Or will we just see the next pivot?

* Spelled Thusly For A Double Dose of That Sweet Sweet Stock Pimping

THE CONTENT CONTAINED IN THIS BLOG REPRESENTS ONLY THE OPINIONS OF THE AUTHOR. THE AUTHOR MAY HOLD EITHER LONG OR SHORT POSITIONS IN SECURITIES OF VARIOUS COMPANIES DISCUSSED IN THE BLOG. THIS COMMENTARY IN NO WAY CONSTITUTES INVESTMENT ADVICE, AND SHOULD NEVER BE RELIED ON IN MAKING AN INVESTMENT DECISION, EVER. THIS BLOG IS NOT A SOLICITATION OF BUSINESS: ALL INQUIRIES WILL BE IGNORED. THE CONTENT HEREIN IS INTENDED SOLELY FOR THE ENTERTAINMENT OF THE READER, AND THE AUTHOR.

We continue to wait for The NaDDir*, and his klown krew, at everyone’s favorite reverse-merger pink sheet Coronacrapper, Cytodyn (CYDY) to actually reveal the top line results from the CD12 study of loserlimab for Severe-to-Critical Chinese Coronavirus Disease. Since The NaDDir* is giving us extra time, we will continue our look back at Cytodyn’s long history of broken, empty, promises. Failing to deliver is a bit of a specialty for the klown krew.

For example, a little over a year ago, we recalled seeing a press release touting both a presentation by Jonah Sacha, PhD., and a new clinical trial in Thailand, testing loserlimab as an HIV Pre-Exposure Prophylactic (PrEP). Try as we might, however, we could not find it on the Cytodyn website, although the press release still shows up on Bloomberg, Yahoo Finance, and other sources. Here is the timestamp from Bloomberg:

Yet on the Cytodyn website there is now a gap where the Jan 27th press release used to be:

Why did it disappear? Reading on from the headline we might get some clues:

First, Jonah Sacha is not a medical doctor, his work is on animals. Any abstract by Sacha would have nothing to do with the use of loserlimab as PrEP for HIV in humans. But more importantly, outside of this press release’s claims, there is no evidence of this presentation at the CROI conference in 2020. Here are the details from the press release:

Try as we might, we could find no record at all of such a presentation on the CROI 2020 website. Not in the Abstract E-Book, not in the online search tool. Nothing. Don’t believe that? Try it for yourself here.

Somewhat amazingly, four months later, back when the company took live questions on their conference calls, The NaDDir* stumbled through a weird excuse as to why this never materialized:

Surely then, the Cytofans would argue, that was just a mistake and rest of the press release was true. The part about doing a PrEP study with loserlimab in Thailand:

You remember, the one they had been touting since at least June 2019:

Would you be surprised to learn that the Thai PrEP trial, like the CROI presentation by Sacha, never happened?

So there you have it. Just one of the press releases from 2020 that Cytodyn would rather readers forget. There are well over 100 more press releases from 2020 for us to explore together, as we await the denouement.

*Spelled thusly for a double dose of that sweet sweet stock pimpin’

THE CONTENT CONTAINED IN THIS BLOG REPRESENTS ONLY THE OPINIONS OF THE AUTHOR. THE AUTHOR MAY HOLD EITHER LONG OR SHORT POSITIONS IN SECURITIES OF VARIOUS COMPANIES DISCUSSED IN THE BLOG. THIS COMMENTARY IN NO WAY CONSTITUTES INVESTMENT ADVICE, AND SHOULD NEVER BE RELIED ON IN MAKING AN INVESTMENT DECISION, EVER. THIS BLOG IS NOT A SOLICITATION OF BUSINESS: ALL INQUIRIES WILL BE IGNORED. THE CONTENT HEREIN IS INTENDED SOLELY FOR THE ENTERTAINMENT OF THE READER, AND THE AUTHOR.

Another day, and we finally get a press release from The NaDDir* and his klown krew at everyone’s favorite reverse-merger pink sheet Coronacrapper, Cytodyn (CYDY). Sadly they have yet again denied the world the top line results from the CD12 study of loserlimab for Severe-to-Critical Chinese Coronavirus Disease. Instead, seemingly to break the monotony, this morning they decided to tell Cytofans everywhere (and we count ourselves among the fans of this ever more crazy circus) to go pound sand for another two to three weeks. Yet again we wait. To call a Cytodyn press release, like the one this morning, curiously worded, is redundant at this point:

Everyone at HQ is quite surprised that The NaDDir* needs two to three more weeks to craft a new story for the suckers. At least this gives enough time for Fife to get his next monthly $7.5mm payment before the bottom falls out.

*Spelled thusly for a double dose of that sweet sweet stock pimpin’

THE CONTENT CONTAINED IN THIS BLOG REPRESENTS ONLY THE OPINIONS OF THE AUTHOR. THE AUTHOR MAY HOLD EITHER LONG OR SHORT POSITIONS IN SECURITIES OF VARIOUS COMPANIES DISCUSSED IN THE BLOG. THIS COMMENTARY IN NO WAY CONSTITUTES INVESTMENT ADVICE, AND SHOULD NEVER BE RELIED ON IN MAKING AN INVESTMENT DECISION, EVER. THIS BLOG IS NOT A SOLICITATION OF BUSINESS: ALL INQUIRIES WILL BE IGNORED. THE CONTENT HEREIN IS INTENDED SOLELY FOR THE ENTERTAINMENT OF THE READER, AND THE AUTHOR.

For a month The NaDDir* and his klown krew at everyone’s favorite reverse-merger pink sheet Coronacrapper, Cytodyn (CYDY), have kept the world waiting for the top line results from the CD12 study of loserlimab for Severe-to-Critical Covid-19. Keen readers already know that, regardless of the outcome, an EUA for loserlimab in the USA is virtually impossible at any time (see why here). While the world waits, the curmudgeons at BuyersStrike! HQ thought it might be fun to look back at some of the other developments Cytodyn has promised and never delivered.

It has been a little over seven weeks since Cytodyn announced what they claim to be an “Open Label Extension” would be added to the CD12 study. The hype began on Christmas Eve, 2020:

A follow-up press release was issued a few days later,on the 28th:

Leaving aside Cytodyn’s complete misunderstanding and misrepresentation of what an Open Label Extension actually is, for such a monumental achievement that warranted two press releases, there was no corresponding 8k filed with the SEC. What does that mean? Simply put, any time you see a press release but no corresponding 8k, the “big news” is actually completely immaterial.

An 8k is not the only thing missing. Even though it has been 6 weeks since the protocol amendment has been supposedly accepted by the FDA, there is no evidence of any OLE for the CD12 study on Clinicaltrials.gov. See for yourself here. The most recent updates to the CD12 trial records are from mid-November, 3 months ago!

Does the OLE exist only in Cytodyn press releases and The NaDDir’s* imagination?

*Spelled thusly for a double dose of that sweet sweet stock pimpin’

THE CONTENT CONTAINED IN THIS BLOG REPRESENTS ONLY THE OPINIONS OF THE AUTHOR. THE AUTHOR MAY HOLD EITHER LONG OR SHORT POSITIONS IN SECURITIES OF VARIOUS COMPANIES DISCUSSED IN THE BLOG. THIS COMMENTARY IN NO WAY CONSTITUTES INVESTMENT ADVICE, AND SHOULD NEVER BE RELIED ON IN MAKING AN INVESTMENT DECISION, EVER. THIS BLOG IS NOT A SOLICITATION OF BUSINESS: ALL INQUIRIES WILL BE IGNORED. THE CONTENT HEREIN IS INTENDED SOLELY FOR THE ENTERTAINMENT OF THE READER, AND THE AUTHOR.