Questions, No Answers - An Anecdote Here’s a situation where I raised questions and the responses I got, or didn’t get, concerned me.
Dr. Deborah Rathjen made a point of providing information in corporate presentations (CP) about the potential for xB3-001 becoming a standard of care (SoC) for HER2+ breast cancer. The information can be found in a number of versions of the CP, including on pages 19 and 20 of an April 2020 CP.
Discussion of xB3-001 as the SoC for breast cancer gets a little involved. It’s clear that an FDA-approved xB3-001 could be the SoC for HER2+ brain tumours (metastases). There is no current treatment for those metastases.
Herceptin can kill undetectable HER2+ metastases. The little tumours are only a few cells in size and are called diffuse tumours. Herceptin molecules can nevertheless attach themselves to the cells and kill diffuse tumours in a proportion similar to its kill rate with larger tumours of the same type.
That means that xB3-001 can likely do the same in the brain. It should be able to kill both detectable (large) tumours and undetectable (diffuse) tumours.
Also, xB3-001 should be able to kill HER2+ tumours throughout the body. It is, after all, a version of Herceptin and xB3 should not change its method of action or efficacy, other than to improve its efficacy (for reasons associated with the LRP-1 receptor).
From all of this it follows that if xB3-001 were to be used as the first treatment for primary breast cancer, that like Herceptin, it could treat all HER2+ tumours in the body - the primary tumours, metastases and diffuse tumours, and in addition, do the same thing in the CNS with brain metastases of all kinds. After all, 94% to 96% of xB3-001 stays in the body and 4% to 6% is delivered across the BBB.
From this the case can be made that xB3-001 could be the standard of care in all cases of HER2+ cancer patients and replacing Herceptin as SoC. That’s about a US$7 billion annual market.
Indeed, Bioasis had Bluestar, as part of their contract, prepare assessments of the potential annual revenue possible from xB3-001 for the treatment of brain tumours and as the standard of care replacing Herceptin for all HER2+ patients for which Herceptin is indicated. The numbers are in the corporate presentations, appropriately discount as a matter of good projection practice.
But there’s a little issue with the math. Herceptin is initially dosed in a patient at 8 to 10 mg/kg. That’s the amount of drug per kilogram of body weight required for first treatment. With xB3-001, about 4% to 6% goes to the brain. So if the dose is calculated at, say, 9 mg/kg throughout the body, and if the brain is only 2% of body weight, then the brain will be over-dosed by a factor of 2 to 3 times. The brain will receive a dose of 18 mg/kg to 24 mg/kg. (4% to 6% of the dose going to only 2% of the body)
So the question is this. To deal with the over-dosing situation, should the amount of xB3-001 be reduced by one third to one half in order to get the right (9 mg/kg) dose to the brain, and with regular Herceptin being used to top up the body’s requirement.
This means that Bluestar’s SoC revenue projection could be high by a factor of 2 or 3 times.
So I had a couple of questions for DrDR. Could a combined Herceptin/xB3-001 combination be manufactured that could be patented so that Bioasis could retain all of the SoC revenue? Or would xB3-001 be able to capture only a third to one half of the SoC revenue? Should the corporate presentation be fixed to reflect these considerations?
The question hardly registered. She wasn’t even interested in contemplating it, let alone discussing it with me. I had received the cold shoulder from her before. She actually told me rhetorically one time that who was I to ask her science questions, that she’d been working with monoclonal antibodies since Christ was a cowboy. I got no answer.
It was clear to me that she had never contemplated the question, and may not have even understood my questions. I offered to send her my spreadsheets calculating brain/body concentrations based on xB3 vs non-xB3 delivery, adjusted for frequency of doses and the cascading effects of the half lives of the Herceptin/xb3-001 drugs in the body and brain.
Nope, she didn’t want those. They’re pretty good spreadsheets. I still have them, of course.
I asked Mei Mei at a roadshow. She had never contemplated the question. I understood that because her expertise is in the use of xB3 as a delivery mechanism, and the construction of xB3 fusion proteins and conjugates. We agreed that the question would likely need input from a physician, an oncologist.
Meanwhile, I believed then and still believe that the US$7 billion annual revenue projections are incorrect and should be lowered by a half to two thirds. It’s still a lot of money, and it’s certainly worth pursuing.
I think Ellipses thought it was worth pursuing, up to some point, when they disappeared, despite a presentation being leaked saying that a deal had been done with Ellipses. By the way, I think it’s possible that Ellipses and Bioasis were introduced to each other by a member of the Bioasis Medical Advisory team,
Javier Corts, M.D., Ph.D.. He was also a consultant to Ellipses, among many other companies.
Satisfaction was always difficult to obtain by asking questions of DrDR. She controlled the information and wasn’t going to let any outside forces get it or change it. I think it’s going to bite her, big time. I don’t think she’ll be much of an asset to whoever gets xB3. I don’t think she knows enough. But simply getting xB3 into the hands of others may be enough for those others to keep her around.
Time will tell. I think she knows one thing. She knows xB3 works, which is why things are going to come down the way they look like they’re gonna come down. Rathjen wins. Bioasis shareholders lose.
jd