0:10
Shenzhen Huayuan Biotechnology Company is an RNA therapeutic startup.
0:14
It makes RNA drugs against RNA targets in type 2 diabetes and cancer.
0:20
We're located in Shenzhen, China, just north of the Hong Kong, China border and currently running through the last of our two million U.S.dollars angel VC funding that we got in 2021 with 15 employees.
0:34
The Human Genome Project finished in 2003 its main take home message is that protein coding genes are just 1.5% of the 3.3 billion base human genome sequence.
0:47
I was a part of the ENCODE consortium that succeeded the genome project.
0:50
We discovered that humans have more non coding RNA genes than coding RNA genes.
0:55
And now we know that approximately 2/3 of human genes are long noncoding RNA.
1:02
So our understanding of the RNA world progressed from this in the 1960s.
1:07
Life is based on DNA which uses RNA to make proteins.
1:13
And now we know that life is just RNA that interacts with other RNA all over the place and just sometimes uses proteins.
1:19
So even though most human genes are non-coding, most pharma companies focus on protein coding targets and small molecules, but not us.
1:29
They do that because long noncoding RNA genes are crazily complex and many of these genes are new in evolution.
1:39
They are primate specific.
1:41
They exist in humans and monkeys but not mice.
1:44
But we have surmounted those barriers to entry and we have gone from genome wide association studies of significant disease associated single nucleated polymorphisms to direct druggable long noncoding RNA targets.
1:59
Not just stupid little markers that are allegedly always linked with something else that people ask millions of dollars for and can never find.
2:05
We don't do that.
2:06
We find the targets and we drug them.
2:08
So we perform disease agnostic discovery of all long noncoding RNA exon SNPs from all genes of 920 different human diseases.
2:18
And when we sorted them we found that our top hit was in the previously uncharacterized long non coding RNA gene we call target number one.
2:26
It was associated with T2D and diabetes and expressed only in the liver in over 50 different gene was data sets.
2:32
This is the top number 3 cause of a diabetes NFLD and Nash in the genome wide Manhattan plot in European Americans and in the top ten in African Americans.
2:43
And we use short interfering RNA because antisense sequence based technology is the only way from gene sequence to drugs.
2:51
Everybody's promising sequence-based drugs we acquire and actually deliver them.
2:56
So first we started with human cells.
2:58
We knocked down this RNA.
3:00
We show that the knockdown of the RNA increases the level of the mRNA target of this long non coding RNA and significantly that this increases the conversion of glucose into glycogen.
3:12
High fasting glucose bad diabetes.
3:15
We take glucose out of the blood deposited in the liver as glycogen, lowering glucose level more than twofold upregulation of the enzyme that's responsible for the glucose to glycogen conversion therapeutic implication this can replace insulin.
3:32
Our target niche at Huayuan are the vast majority of the tens of thousands of human long non protein coding RNA genes that are primate specific.
3:42
So after basic safety and toxicity was done in the mouse data not shown for reasons of time, we proceeded to animal trials of our anti LOC number, whatever candidate siRNA drug in the cynomolgus monkey Macaca fascicularis monkeys in China.
3:58
One of the reasons I'm in China and not in the US anymore is that a monkey in China costs less than a mouse in the US.
4:05
Without any exaggeration.
4:07
Numbers cross checked with US academic and industry colleagues. 10,000 U.S dollars per animal per six months of work at a highly competent, completely above board Shenzhen based CRO.
4:16
This is one of our key advantages.
4:18
But we are not an outsourcer doing other people's drugs on monkeys.
4:21
We are leveraging our location in China to test our drugs in monkeys.
4:26
So first we took monkey cells and we showed that monkey primary hepatocytes behave exactly the same as human primary hepatocytes when it comes to knock down of this target.
4:37
After we confirmed that we gave our drug to live healthy monkeys and we did monthly micro needle liver biopsies showing that the two different dosages of the drug detected during qRTPCR validates the knock down of the monkey ortho of our target.
4:55
To make a long story short, after we did this for six months in six healthy animals, we saw reduced fasting glucose, increased level of the desirable mRNA downstream target of this non coding RNA and interestingly reduced HbA1C.
5:09
That's a very desirable marker.
5:11
So in here you can see 2 normal glucose level monkeys and one pre diabetic monkey with elevated glucose level and you can see how our drug knocks down the glucose level into the normal box.
5:23
Same with A1C, you even see slight A1C decrease in the healthy monkeys.
5:27
But hey, we're not done yet.
5:29
Now we have a sick monkey.
5:30
This is our main result obtained on like the last drags of the pre serious a money.
5:35
And now I'm showing you a monkey that is sick.
5:38
This is a monkey diet induced type 2 diabetes model in cynomolgus monkeys a fat monkey.
5:45
But after taking our drug just once, it became a flat monkey.
5:49
Its BMI and body weight decreased of both by over 10% after two weeks and stayed that way.
5:55
We followed it up after one month on our drug.
5:58
Here's the best despite continuing on the high fat diet, GLP 1R agonist.
6:04
All right, Ozempic, all right, people take 10 times the recommended dose.
6:08
Crazy sacrifices, nausea, vomiting, tearing themselves upside out.
6:12
We don't need to do that.
6:14
Our drug once a year beats Ozempic without the side effects because RNA is sequence specific.
6:20
Protein based drugs are not.
6:22
This is the Ozempic killer.
6:24
We currently have 3 patents, so this is in mainland China and competitor analysis.
6:28
I don't want to read this table.
6:29
I know we don't have the time, but basically the problem with GLP 1R agonists in ability is non specificity side effects prohibitive cause self-injection regimen as opposed to once a year injection at the doctor's office and these are very inconvenient drugs.
6:47
Also RNA costs very little to synthesise here you have a lot of upfront cost actually making the drug.
6:53
We believe that our drug for treatment of T2D and obesity can out compete current GLP 1R agonists.
7:03
Bottom line, we have just presented to you a transformative RNAi based treatment of T2D obesity and possibly although we have not worked on this, non-alcoholic fatty liver disease and non-alcoholic steatohepatitis.
7:18
They recommend that the regimen shall be a once a year injection and the potential is obvious.
7:23
First of all, this drug can replace insulin because it goes completely around the insulin resistance pathways in diabetes.
7:30
It basically activates an endogenous enzyme that takes glucose out of the blood that converts into glycogen.
7:37
And we dare say, and I know there's some Novo Nordisk people at this meeting somewhere that this is a candidate Ozempic-killer for obesity, fat monkey, flat monkey without the side effects and without the cause and inconveniences.
7:49
So that's just one target, our current lead target, a primate specific long non-coding RNA.
7:54
I got 100 other targets in type 2 diabetes, obesity and even breast cancer and epilepsy.
7:59
So what are our current priorities at Shenzhen Huayuan.
8:03
All of the work I showed you in vivo in monkeys was done in LNPs.
8:07
We want to move away from them and repackage into either exosomes or GalNAc for better human safety.
8:13
Complete an in vivo trial on monkeys.
8:16
After we repackage filing an INDA new drug application in China and start probably a small phase zero than phase one human clinical trial.
8:25
And the reason we are in the start of showcase and not a regular talk is that we are going for a series A.
8:33
Our table is at the 33,34,35 area of the startup zone.
8:36
Feel free to stop by tomorrow during the AM break.
8:40
Thank you.
8:40
We are an innovative, unprecedented, primate specific lncRNA targeted siRNA based company that solves the problem of diabetes and obesity.
8:49
We look forward to your participation and thanks in advance to any representatives of venture capital or funds investing in biotech from the Boston area who might be in the room.
8:58
Thanks to my collaborators, CEO of the company Doctor Zhang Xiaosong, COO of the company Doctor Weizhong Wang and the entire team in Shenzhen.
9:07
Key collaborator Erica Kleinbrink from McGill University is back there in the room, and you can e-mail me at Huayuan Biology or at my Wayne State address.
9:14
Now, no commercial science happens without public science.
9:18
That's an important point to make here in the US these days.
9:21
All of my basic work in humans that led to the development of this target in live monkeys was supported in 2014 and 2019 by my NIH New Innovator Award from the Director of the NIH, $2.3 million more than any private investment we ever got.
9:37
Thank you for your attention.