DelMar Pharmaceuticals, Inc. Edited Transcript of Key Opinion Leader Event

DelMar Pharmaceuticals, Inc.

Edited Transcript of Key Opinion Leader

November 22, 2019 at the Annual Meeting

of the Society for Neuro-Oncology

Saiid Zarrabian, President and CEO of DelMar Pharmaceuticals

Dennis Brown, Chief Scientific Officer of DelMar Pharmaceuticals

Greg Johnson, Acting Chief Operating Officer of DelMar

John de Groot, M.D., professor

and chairman ad interim, Department of Neuro-Oncology at The University of Texas M.D. Anderson Cancer Center

David Reardon, M.D., clinical

director of the Center for Neuro-Oncology at the Dana Farber Cancer Institute and professor of Medicine at Harvard Medical School

Tim Cloughesy, M.D., professor

of neurology at the David Geffen School of Medicine at the University of California, Los Angeles and member of the UCLA Brain Research

Institute and Jonsson Comprehensive Cancer Center.

Nicholas Butowski, M.D., Neuro-Oncologist

practicing at UCSF Medical Center in San Francisco, Calif. and director of translational research in neuro-oncology at

the Brain Tumor Center

Zhong-ping Chen, M.D., founder

chairman of the Department of Neurosurgery/Neuro-oncology at Sun Yat-sen University Cancer Center, China and lead investigator

of the Company's Phase 2 clinical trial of VAL-083 in first-line treatment of MGMT-unmethylated GBM

Naureen Quibria, Ph.D., Equity

Research Associate, Maxim Group - Moderator

Mr. Zarrabian: Good afternoon everyone. Please be seated

and we will start this meeting. Thank you very much for attending tonight. So, to start with, my name is Saiid Zarrabian. I'm

president and CEO of DelMar Pharmaceuticals and we set this meeting up in order to be able to tell both the scientific community,

but also the investment community, about the achievements of DelMar. Before we start, I would like to ask every member of the panel

here to just briefly give their name and their affiliation so everybody in the audience knows what their job titles are. And then

we will get going with the presentation. Dennis, we will start with you and Greg and then we will go to the panel.

Dr. Brown: Thanks, Saiid. I would like to thank everyone

for coming. All these efforts, they take a long time and need a lot of people to help out to make things happen and I appreciate

everyone coming today and seeing where we are and giving some insights on what we should think about for the future. So, I am Dennis

Brown. I was co-founder of the company and currently the Chief Scientific Officer.

Mr. Johnson: I am Greg Johnson and I am acting Chief

Dr. Quibria: I am Naureen Quibria and I am with Maxim

Group. I'm an Equity Research Associate.

Dr. Cloughesy: Dr. Tim Cloughesy. I'm a Neuro-Oncologist

Dr. Chen: I am Zhong-ping Chen at Sun Yat-sen University

Cancer Center and I am a surgeon, and also the principal investigator on DelMar's clinical trial being conducted in China.

Dr. de Groot: My name is John de Groot. I'm a Neuro-Oncologist

at MD Anderson in Houston.

Dr. Butowski: Nick Butowski Neuro-Oncologist at UCSF.

Mr. Zarrabian: Thank you very much. With that I would

like to ask Dennis to start with the slide deck, we have a couple of slides that Dennis is going to present first about the compound

itself, VAL-083 and then Greg Johnson who is our acting Chief Operating Officer is going to present a high-level view of the data

that was presented today through the SNO Posters and 8-K early this morning. Thank you, Dennis.

Dr. Brown: Thanks, Saiid. Well again, thank you very

There are a lot of scientists and doctors here trying to help

people solve some problems that are very critical for patients with a very difficult disease, GBM. So I've been involved

with looking around the world to identify new drugs for about 45 years now and I was, I got to be lucky enough to come out to California

about 37 years ago when I had the opportunity to commute from Stanford to UCSF to work with Victor Levin to learn about drug discovery

and development. And in those days, I was part of a really remarkable program with the NCI which was really the critical organization

that was looking for compounds, testing them, and moving them to clinical trials. Some luminaries are here who have done a lot

of work in this area and what I was always impressed about was the level of intellect and the commitment to trying to find new

opportunities from the chemistry, the biology, moving things up in decision networks to getting them into the clinic.

And so, over all those years I was always intrigued by how much

work had been done and the level of sophistication. But there's always a move to keep moving on so when I was at Stanford

in the 80s most of the work that was done was mostly small chemical drug discovery. There was a discovery of cisplatin about that

time and that was a game changer. You got a metal that can somehow do something significant in cancer. And there was another series

of molecules that were damaging DNA and some of them are the mainstay of the therapy for brain tumors. And those are alkylating

agents that attack DNA. And the drugs that the clinicians use today Temozolomide, BCNU CCNU all came out of the development of

NCI's primary work and work by thinktanks such as the Southern Research Institute.

But in those days the biology was not as powerful as it should

have been so the mechanism of action was always unclear. What exactly was it doing to the cell? And people moved along and everyone

felt there would be a next generation product, an antibody or a signal transduction effect or some other vaccine system that would

solve this problem of brain tumors. And there has been progress but what was always interesting to me was that there were agents

and other opportunities that were left on the side of the road. They were not formally developed, or the biology was not good enough,

there was always some other kind of limiting problem. And VAL-083 really represents that, VAL-083 was brought to the United States

by Victor Levin who went to Budapest, Hungary and met the chemist that worked on it and he saw this molecule as being somewhat

interesting and brought it back to the United States and it became the subject of numerous clinical trials. And what was interesting

about the molecule is this. This is the molecule we have been working on. This is really a sugar that has been derivatized, it

has epoxide groups at both ends, and they're very reactive but they have a propensity to bind to DNA. And in those days,

they couldn't quite discern the difference between what this compound did and what nitrosoureas did.

They knew they were binding to DNA causing strand breaks, but

they didn't discern if there was anything different in the mechanism. So, the molecule, aside from not only being from Eastern

Europe, had a weak patent position on it and people kept moving along. They kept thinking there would be a next generation molecule

that would be certainly a lot better to cure brain tumors. About 10 years ago, I came across the drug in China and it was already

approved in China for lung cancer and CML. So, I was very intrigued that the Chinese government, and the scientists there felt

there was something valuable there. So, we went back to look at it and went to see the companies developing it and brought the

compound back to the United States. We started working with UCSF and Nic and Dr. Burris at Sarah Cannon, and ultimately at MD Anderson,

to see if there's something interesting.

We went back and did some molecular biology with some really

wonderful scientists at UCSF, MD Anderson, and University of British Columbia and we started to discern that there's a difference

between Temozolomide's effect on cancer cells and this drug. VAL-083 binds to the N7 of guanine and Temozolomide, which is

a monofunctional alkylating agent, causes single alkylation damage at the 06 of Guanine. So Temozolomide which is a pro-drug has

to open up, has to get up here, and it typically just has one fist to work with. But what was learned in the last 25 years is that

it's readily repaired by an enzyme called MGMT (methylguanine methyltransferase) so that enzyme which is highly expressed

in a high percentage of brain tumor patients can quickly mop up that damage and it's as if that patient did not receive any

So, what we were able to discern is VAL-083 is a bifunctional

alkylating agent, a bifunctional crosslink on DNA is formed which is somewhere, here, up in here and in the N7 position and this

is extremely resistant to the effects of MGMT (methylguanine methyltransferase). And that became intriguing, so we

started talking to clinicians, we started to do some more experiments. And we started to compare the differential responses in

numerous GBM cell lines that were sensitive to Temozolomide. For example, they were methylated, and we looked at differential IC

50's between what our drug would do relative to Temozolomide and you can see we had differences in IC 50's that we

would be able to achieve in comparison to temozolomide to kill half of the tumor cells . For VAL-083, IC50's of approximately

2-5 micromolar were observed relative to 10 micromolar with Temozolomide for the methylated cell lines. And when you went into

the unmethylated cell lines we had about equal sensitivity between the two different genotypes, but you can see with Temozolomide

you would require up to 100 micromolar to achieve equal cell kill. So, this is the type of data that we were able to use to start

speaking with clinicians, and to start looking at ideas of how we might move forward. And with that we went back, we started to

manufacture the drug, started going back to the FDA, and started the design elements for some clinical trials. What I would like

to just finish up is that we've been able to be involved with some really wonderful doctors, and scientists that have helped