Possibly important new drug for breast cancer

I often say these articles are not official Deloitte research. I really mean it this time. This is purely my own interpretation of breaking news in biotech. It is intended only to explain some complicated issues and is definitely not investment advice.

By noon today, Greenwich Life Sciences (GLSI) was trading over $80 per share, which was up from just over $50 yesterday, which was up from $5 on Tuesday. With about 12 million shares outstanding, it has gone from a market cap of about $60 million to about $1 billion in a couple of days. And it’s all because of a poster.

I used to be a biotech investor and venture capitalist and attended a number of cancer conferences. Normally, the most important and exciting papers were scheduled well in advance, and presented in the plenary sessions, with 10,000 people sitting and standing in the biggest room available. But sometimes, late breaking data was presented as a simple poster: no speech, no academic paper, no big hall, just a 120 cm by 240 cm poster jammed with all the details one can fit (usually with a press release too.) To be clear: there is nothing wrong with presenting important and exciting information via a last minute poster. It isn’t the majority of breakthroughs, but it absolutely does happen and nobody holds it against the news.

Above is the poster presented by Greenwich at the 2020 San Antonio Breast Cancer Symposium (SABCS), with the somewhat intriguing title in the press release of:

Greenwich LifeSciences Announces Poster Presentation of Five Year Data for GP2 Phase IIb Clinical Trial, Showing 0% Recurrence of Breast Cancer

“0% recurrence” is obviously exciting. Normally I wouldn’t bother to write an ‘explainer’ article like this, but media coverage so far has focused on the dramatic share price rise, rather than the science and meaningfulness of the data. Given that I have (far too many) friends who have been diagnosed with breast cancer, and the possibility of misinformation/misinterpretation, I am going to walk through my own personal take on the poster. This is NOT financial or investing advice, but rather a guide for people who care about progress in treating this kind of cancer.

Breast cancer and HER2 receptors

Breast cancer is not a single disease, but a group of diseases. In 1987, Dennis Slamon and team published a paper showing that some breast cancers had high expression of an oncogene (a gene associated with cancers) called HER2/neu (usually shortened to HER2), and that cancers that overexpressed this gene were unusually aggressive. To be clear, all breast tissue has some HER2 oncogenes, but some have much more than others, and those are called HER2 positive.

For a while, having a breast cancer be diagnosed as HER2 positive was a bad thing, and indicated a poor prognosis for survival. But having an oncogene target meant that scientists could try to hit that target, and they did. In 2005, trial results for a drug called Herceptin? (generic name trastuzumab), showed blockbuster improvements in five year survival, the gold standard for cancer treatment. Since then, trastuzumab is almost universally used on patients with HER2 positive breast cancers, improving ten year survival from about 75% to about 84%.

There are a number of other drugs that are approved to treat HER2 positive breast cancers, and more in the pipeline, with Greenwich’s drug (called GP2 for now) being one of them. One really critical point to make is that all of these drugs are targeted therapies, and only work on cancers that are HER2 positive. If there are too few HER2 receptors, the drugs have no effect. That is true of Herceptin, and would likely be true of all the other drugs in the clinical trial pipeline too, including GP2.

Which breast cancers are HER2 positive, and how many?

As you might guess, it isn’t like people with too many HER2 receptors have an extra leg or anything that makes it easy to identify. These are tiny little receptors, and hard to detect. The most commonly used test is an immunohistochemistry (IHC) test of tissue from a biopsy or surgery, which is then scored 0, 1+, 2+ or 3+. Remember that all breast cancers have some HER2, the diagnosis is looking for overexpression of the receptor.

• 3+ means the cancer is HER2 positive.
• 0 or 1+ means the cancer is HER2 negative
• 2+ means equivocal. Sometimes these are tested with another diagnostic tool called FISH, which is more expensive and slower, but thought by many to be more precise.

In general, 3+ would almost always be given HER2 drugs such as trastuzumab, 0 and 1+ would almost always not be given HER2 drugs…and (oncology is complex and hard) 2+ might be given the drugs or might not.

About 20-30% of all breast cancers are diagnosed as HER2 positive. Young women with breast cancer are more likely to be HER2 positive, which is bad (it is more aggressive and more likely to recur) but also good (since there are effective treatments for HER2 positive cancers). All other things being equal, oncologists care much more about being able to treat cancer in an otherwise healthy 30 year old than in a 90 year old. (Worth noting here that men can also get breast cancer, including HER2 positive breast cancer, although it is relatively rare: less than 1% of all breast cancers are in men.)

Analysing the poster

1. By and large, it looks good. “Phase IIb clinical trial was a prospective, randomized, single-blinded, placebo-controlled, multi-center (16 sites) trial led by MD Anderson Cancer Center for a Phase IIb clinical trial.” MD Anderson is first rate.
2. Various media stories are describing this as a 168 person trial (which it was) with 100% survival for those treated with GP2 (which is inaccurate.)
3. Of the 168 patients in the trial, only 96 were HER2 3+ (aka HER2 positive). 50 HER2 positive patients were given placebo and GM-CSF (a drug often given to HER2 breast cancer patients) and 46 HER2 positive patients were given GP2 plus GM-CSF. The 100% survival benefit was only seen in the HER2 3+ patient subset, there was no survival advantage in the group of patients who were HER2 1+ and 2+.
4. The problem is not that GP2 only worked in the HER2 3+ group. It was only supposed to work there, and it would have been weird if it had worked in the other group. The problem is that one needs to be careful about looking at a 96 patient analysis. It’s just a really small number. Back of my napkin, if even one or two people in the GP2 treatment group had died, and if one or two in the placebo group hadn’t died, the survival difference between the two arms of the trial would be much less impressive, and possibly not even statistically meaningful.
5. Greenwich is doing the right thing, and pushing forward for a larger Phase III trial to confirm the exciting findings so far…but that is going to take a while.
6. There is one other thing that caught my eye from Table 1 of the poster. In the HER2 positive groups (in red) the placebo and treatment arms were generally well matched…except for trastuzumab use. 93.5% of the GP2 arm had trastuzumab use, while only 84% of the placebo arm had. That’s a 10 percentage point difference, and given the 5 year survival difference from Figure 1 was also about 10 percentage points, I do wonder if this variable might account for some or all of the survival improvement.

Some other things

This whole thing is unusual from a capital markets perspective. (That’s not necessarily a bad thing: breakthroughs can come out of nowhere.) This was a microcap company on Tuesday, so small that even the company that took them public in September doesn’t provide research coverage yet! I imagine a lot of top flight biotech analysts are getting called by their institutional investor clients, and are providing their unofficial views. But the rule in the investment research business is that analysts aren’t allowed to opine publicly and in print on stocks they don’t cover, so the average person has no access to informed analysis.

Which is why I am writing this post. Not to provide investment advice, but to provide some context on a fraught topic. About 300,000 women per year in the US and Canada will be diagnosed with breast cancer in 2020, and over the last decade that would be 2-3 million diagnosed and worried about recurrence.

They are going to read stories about a possible “cure” for breast cancer. This post is for them.

What does this all mean?

1. For the 70-80% of those with breast cancer that is not HER2 positive, this (sadly) means nothing for them.
2. For the 20-30% who are HER2 positive, this looks like it could be very good news.
3. That said, as a result of various HER2 treatments, the ten year survival rate was already about 85%, which is pretty good.
4. But 100% is even better, so fingers crossed.
5. I have seen some bad posters, and (although I admit I am out of practice, not having been to a cancer conference since 2004) I don’t think this one is riddled with all kinds of red flags.
6. My main concern is that the darn trial was just so small. I have friends with this disease, and I would say one thing to them and one thing only:

“Don’t get too excited about trial results when there were only 96 HER2 positive patients across two arms.”

What about the investment implications?

No idea. I don’t do that kind of analysis anymore.