Skip to playerSkip to main content
NovaStream
  • 2 days ago
Transcript
00:00I will do everything in my power to save my debt, so I appeal to you.
00:15I will look at the brain, it's truly a breakthrough.
00:21One in five people will suffer from cancer in their lifetime.
00:39Many will not survive it.
00:46For most cancer patients, the only hope they have is chemotherapy.
00:54Chemotherapy delivers toxic chemicals to the body randomly, affecting not only the cancer cells but also healthy cells.
01:04The holy grail of cancer research is to find a solution to the dangerous side effects of chemotherapy.
01:12Scientists Amanchu Brumbat and Jennifer McDiamond are about to realise their dream as they begin clinical trials on a discovery their peers are claiming will be the magic bullet many have been searching for.
01:26It is absolutely fantastic.
01:29However, for their small Australian biotech there are many pitfalls.
01:34The cost of taking a biotech discovery to market can be a billion dollars.
01:39The process is complex and only about 8% make it.
01:44Even in the face of desperate need in cancer patients, will this small Australian David be able to take on the international biotech Goliath?
01:5620 years ago these two molecular biologists met at night for weeks on end to discuss ideas.
02:15A colleague had just died of horrifying cancer and his dying words challenged the pair to find a solution to the growing problem of cancer.
02:25Jennifer and I were at the hospital and he said, you know, if someone can do it, you can do it.
02:42He pointed his finger like this to us.
02:46You can do it.
02:47You can do it.
02:49I just can't forget his eyes.
02:52He said, it's just, it's alive.
02:56You know, it's just the impact of that.
02:59It's just, it's horrific.
03:01And I thought, a stupid man, what have I done with my life?
03:07So strongly motivated by the needs of cancer patients and believing they had a revolutionary idea,
03:13they risked everything and set up their own laboratory which they called Ingenic.
03:20This small biotech company with its dedicated staff has produced compelling evidence at lightning speed to verify its discovery.
03:30Imagine, I have like 100 mice per experiment and then it went on to a trial for, with the monkeys and then we went to dog trials and now if we go to a human trial, imagine from a mouse to a human within the span of seven years.
03:48So to me that is very exciting.
03:56Scottish-born immunologist and former Australian of the Year, Ian Fraser has experienced first-hand the process of commercialising science.
04:05He created the vaccine Gardasil for cervical cancer.
04:08There's always a risk that a good invention will not make it to market.
04:13The good science may not easily lend itself to getting out into the market place.
04:19People may not understand the need for it yet or the potential may not be there.
04:23In the next month, the Ingenic Dream Vector, or EDV, will be injected into a human for the first time as the trial process begins.
04:32Never before has a bacterial nano-cell been used to carry chemotherapy into the human body.
04:38The pressure is really mounting. Obviously we've got to get it into people, but it's very scary.
04:44Nothing like this has been given to people. It's not a me-too drug. That's what's keeping me up at night.
04:50Cancer drugs cause horrendous toxicity. So somehow, if you're going to put a drug inside the body, if you could encapsulate it and make sure that it doesn't go into normal cells,
05:04then you need something to pack it. Then you also needed something that's going to prevent that ball from going into normal cells.
05:18So therefore, you needed something on its surface that's going to lock in a cancer cell and not lock into a normal cell.
05:29But the more I looked at it under the microscope, the more you felt that this was not just any ordinary particle.
05:40This was something quite remarkable.
05:43It had a complete membrane structure. It was non-living. It had a capacity inside. It was empty. It's like a house. You could live in there. Something could go in there.
06:02It had structures on its surface. Hair-like structures. These are very important structures because to that you could attach other molecules.
06:14And those molecules can then target something else. And suddenly you could see that whole picture unfold.
06:21Ingenic have published their work recently in Nature Biotechnology, which is the prestigious journal in the field.
06:28What that really means is that it has been rigorously peer-reviewed by a group of other scientists who work in that space.
06:36And they've said, A, this is novel. B, it looks like it works. C, it's really of interest.
06:42Because to get into one of the Nature Group journals, it's got to be top stuff. And what that really says is they've got a winner.
06:49A team of Sydney scientists has worked out a way to kill cancer tumours.
06:53This Trojan horse might just open the gates on a new cancer trip.
06:57Drugs were once considered to be the magic bullet. Now it's the vehicle by which they're given to the patient, taking centre stage.
07:04The international biotech industry is ruthless and cutthroat. And taking science to market is not for the faint-hearted.
07:12So it's a bit wary.
07:15The figure that's widely quoted as the cost for taking a new discovery from the lab right the way through to a product in the marketplace is about one billion US dollars.
07:27A large part of that money is spent in the final studies that will show that the drug works.
07:32But the money is spent over a very long period of time, usually 10 to 15 years.
07:38So quite a substantial part of that money is invested 15 years before there's any prospect of there being a return on it.
07:44Venture capitalist Stuart Wardman Brown is just such a risk-taker.
07:48His company has invested in Ingenic for eight years and he is currently acting as chairman of the board.
07:55For me Ingenic is very clearly a business first and crusading against cancer second.
08:01For other people I can understand that perhaps it's a crusade against cancer and that the business aspects are merely one of the things they've had to do in order to raise enough funds to be able to take that crusade hopefully all the way through.
08:17and have an impact on cancer.
08:21Clearly positive trial results will increase the value of his shears and he wants the science to move quickly.
08:28But not as good.
08:30She is tough.
08:33It may have something to do with that Scottish background.
08:38They go out there in that vicious cold and they will fight to death.
08:44These are valiant fighters.
08:47He has been able to harness a thought process that is almost foreign to me.
08:54You know, he can see the big picture very clearly and develop a thought process which is very exciting to be around.
09:02To prepare for the huge step into human trials, Ingenic has done extensive testing in animals.
09:0927 dogs.
09:1027 dogs.
09:12Nobody goes into a human trial having studied so many dogs.
09:16But we have had to go through all of this because we needed to know for ourselves that was there something that we have missed.
09:28Something that again our conscious mind might have said everything will be fine.
09:32So irrational exuberance is what we have to try to avoid.
09:37However, their successful treatment of dogs is undeniable.
09:41We have got a brain cancer dog that jumps up, grabs the biscuit and, you know, runs around etc.
09:50And when I look at the dog and I feel that this little nano cell went in there and did all those things.
10:01I still look at it in absolute amazement.
10:04And the dog just stares back at me and says, have you got a biscuit?
10:08Dogs get cancer just like humans do.
10:10And these cancers need to be treated just like they would be in a human.
10:14And they behave very much like they do in a human.
10:16So trials that show that a drug works in an animal model where the cancer is a real and spontaneous one are much more likely to be representative of what would happen in a human.
10:27Matilda, come and have a look at your brain scan.
10:32And this is the brain tumour she had.
10:35Clearly inoperable because it's right in the middle of the brain.
10:40So here we have where the brain tumour used to be.
10:43This is following five doses of EDVs loaded with doxorubicin and targeted with EGFR.
10:49The bottom panel shows that the tumour is basically totally resolved in Matilda after only five weeks of EDV treatment.
11:02To have Matilda come in and it's quite a surprise really.
11:04You sort of all of a sudden go, wow, this is actually making a difference.
11:09You know, we've cured a dog and surely the next step is to cure people.
11:15We've got pressure from the investors.
11:19When's it starting?
11:20When's it starting?
11:21When's it starting?
11:22And we're saying, well, you know, a week either way to make sure it's right is not going to make a difference.
11:27The clinical trials are being conducted in Melbourne across three hospitals.
11:36Before this can happen, a totally new piece of science like the EDV is extensively scrutinised by clinical and ethical committees.
11:45Finally, the EDV is cleared for first in world human trials.
11:51This is it. This is the final loophilised EDV preparation that we'll be sending down to Melbourne for the human trial.
11:58Most clinician scientists feel very nervous when they go first into a clinical trial.
12:03It's called first into humans because you just don't know what's going to happen.
12:07You've done all the right homework. You've done everything you possibly can to make sure the product's safe.
12:11You're usually convinced because of the nature of the product that there shouldn't be any problems.
12:16But having actually put a drug into humans for the first time myself on more than one occasion now,
12:21yes, you get very nervous about that and you take every precaution.
12:25And certainly Jennifer and myself are full of fear at the moment.
12:29We feel, is everything going to be all right?
12:34What happens if something goes wrong, somebody gets a reaction?
12:41Such a system has never been trialled before on this planet.
12:47There's plenty to be anxious about as the science moves from the laboratory to the hospital in preparation for the trial.
12:54Not only do the medical costs soar, but the scientists now have to hand over their precious discovery
13:00to the clinicians who carry out the trial.
13:03Professor Mark Rosenthal is on the trials team.
13:07We were excited three years ago, I think when I first met with Jennifer and Hermanshu.
13:12I suppose we're relatively sanguine about the chances that this really will be a success.
13:18It is quite difficult in a way to be an onlooker in your own trial.
13:25But we're not down there holding hands with the patient, which frankly is what I'd like to be doing.
13:30You know, saying, are you all right? Feeling the pulse.
13:33I believe the scientists have to stay well away from the entire program.
13:38They've done their bit. They've made the discovery. They've done the development.
13:43It's now up to the clinicians. And I think it's utterly inappropriate for there to be any link
13:48between the scientists and the clinicians in terms of interpretation of data.
13:52What our public, what our patients want is clear-sighted analysis of what this all means.
14:00But the whole focus of the scientists' research is to help patients.
14:04And after nearly ten years of painstaking research, our team finds it impossible to be too far away from their first patient.
14:12I've been thinking about that woman all the way down, really, and how brave she is.
14:18I reckon you'd see, if there was any problems, you'd see it by four o'clock.
14:22By four o'clock, I would have thought, yes.
14:25You're always battling dogma and preconceived ideas about how cancer therapy should be controlled.
14:33It's a battle all the way to get them to change something, even though it's a clinical trial.
14:38It has taken ten years to begin first in human trials, and today is the culmination of many years' work, and everybody is tense.
14:48The Ingenic team is delivering the first dose, and Jennifer and Amanchu want to be very close in case anything goes wrong.
14:57They've taken a hotel room right next door to the hospital.
15:02They're hopeful the clinicians might relent, and give them access to, or at least information about, the patient.
15:10For now, there is nothing left to do but wait.
15:15It's been the longest five hours of my life.
15:21A chance call from the trial pharmacist, John Barlow, finally brings the news everyone's been waiting for.
15:32He was just over there, just happened to be moseying past there.
15:36Yeah, how convenient.
15:38Picking up something for another trial, he said, yes, right.
15:41But he had a long chat with her.
15:43Oh, yeah, nice.
15:44She's a very charming woman, who's very chuffed at being the first person on the trial.
15:52And she said she didn't feel a thing, still doesn't feel a thing, nothing's happening.
15:57She's just laying around reading, waiting to go home.
16:02By the end of the day, it's time to get back to Sydney.
16:05The team knows the beginning of the trial has been a success, and the first patient has received EDVs without any side effects.
16:13Something really big has begun in Melbourne.
16:18Ingenic now needs a big farmer to invest.
16:22Human testing usually runs over three trials, each bigger and much more expensive than the last.
16:29But even though they are now testing successfully in animals and humans, in order to attract a big farmer,
16:36they will have to take a backward step and produce a test tube result.
16:41What sort of cells?
16:43In the pharmaceutical industry, this is the conventional way to prove that the science is robust.
16:49Yeah.
16:50Can I have a look at cells only?
16:51Yeah.
16:52Dead cells only in there.
16:53And these are lung cancer nasty cells.
16:56I'd wake up sometimes early in the morning and I could imagine what I would like to see under that microscope.
17:03These are the HCP cells.
17:05Yeah.
17:06Okay.
17:07Every cell specifically being hit and I could always imagine there's going to be all these dots.
17:13But failure after failure after failure in experimentation.
17:17For five months we failed.
17:24It is absolutely fantastic.
17:28This is so good.
17:29Yeah, let me have a look.
17:31This is fantastic.
17:32Every cell.
17:33Oh yeah, this is really good.
17:34This is really exciting because today we've been able to show the EDV locking on to the cells,
17:43the cancer cells specifically in great numbers and ready to be engulfed and cause death to the cells.
17:52Even though the first experiment is successful, there's now urgency to repeat it so that pharmaceutical companies are convinced it can be done in any lab.
18:02It's a stressful time for everyone in the company.
18:07The amount of funds required to run this kind of an operation is absolutely massive.
18:13And investor funds cannot keep on supporting this kind of effort.
18:18So we need to partner with a major pharmaceutical company one or more such that in that partnership,
18:26the big pharmaceutical company has sufficient financial muscle to be able to support,
18:31not only support this research, but develop it quickly to get it into the clinical trials and onto the market if they are successful.
18:38But without that partnership, this company could be in extreme danger because we already are aware that there are certain hawks
18:47that there are certain hawks out there whose intent it is that if we run out of money they will swallow us whole.
18:57Jennifer and Namanchu have become aware that some of these hawks are within the ranks of their own investors.
19:05At this point, some investors believe that the scientists should be replaced as managers of the company.
19:12The science is first rate, but you've got really almost a fundamental divergence of the commercial imperatives of the investors,
19:24who want to see this commercialised, and the scientists who want to see the science progressed in accordance with their own view.
19:35The model with the scientists who've got no commercial experience running the commercial development is not often a model for success.
19:46The difficulty is the scientists have to understand the businessman's point of view,
19:49and the business person's got to understand the scientist's point of view, otherwise it doesn't work.
19:54Most small biotech companies that get into trouble early on get into trouble either because they don't recognise they need both bits of the equation to make it work,
20:02and try and do it on their own, either a businessman trying to run the science or a scientist trying to run the business.
20:08Despite opposition in some quarters to their management, Namanchu and Jennifer survived the challenge to their leadership.
20:15They put their case for further funding to their principal investor.
20:20Meanwhile, the human trial in Melbourne is progressing very positively.
20:25While the scientists remain at arm's length, because the science is so new, the clinicians need the scientists to understand the novel technology.
20:34I take a bit of silver.
20:35Cheers.
20:36Cheers.
20:37Cheers.
20:38Cheers.
20:39Cheers.
20:40Cheers.
20:41Cheers.
20:42Cheers.
20:43Cheers.
20:44Right from the beginning, our patent attorney said to us,
20:47If this turns out to be as good as what it sounds on paper, you are going to end up in court somewhere in the future.
20:56As a consequence of the Nature Biotech article, it becomes obvious that an American copycatter is trying to register an aggressive patent.
21:06But Manchu has to counter its claims.
21:09The whole business of patenting itself is a very complex one and getting it right and protecting things will take away a lot of energy from getting on with new science.
21:17Because you've got to get the wording right.
21:19That's what patent attorneys are there to do.
21:21But you've also got to make sure that you've thought through all the possibilities.
21:24Supposing somebody did it slightly differently, would they be able to get round your patent and leave you in a situation where you had a patent but it wasn't actually protecting the thing that you needed to protect?
21:34So I think there's a whole industry growing up around the idea of how can we make money out of patents rather than how can we make money out of products?
21:41When you're dealing with situations where people are dying and there are these sorts of scavengers of society sitting out there smelling money and they go after you on fraudulent grounds, it makes your blood curdle.
22:00After a long night of answering challenges from patent office examiners, Manchu still can't get back into the lab.
22:07God knows who makes these people as examiners in these patent offices and they can virtually destroy your entire company.
22:15Because on false grounds they keep on arguing with you. They keep on arguing and say that no, this is all obvious, you don't have an invention.
22:25And they always think everything is invented in the United States. Nobody else has invented anything.
22:30It is, how can I stop you from getting there? Strangely such people never seem to get cancer.
22:38In the heat of this copycatting threat, the need to keep proving the science takes on an urgency and keeps everybody working around the clock.
22:47What we're seeing here is the EDVs still on the outside, but as they take up the EDVs, the cells aren't able to keep doubling, so eventually they'll die, which is exactly what we're after.
23:01Let's leave it till morning.
23:03In the worst case, we'll see cell death.
23:05We'll see cell death, yeah.
23:06Yeah, if we see cell death, we'll all be happy.
23:08OK.
23:09There are so many emails that have come in about children dying from brain cancer.
23:21And you think, there is no room for resting until we get this out there for such people.
23:34Chairman Wardman Brown arrives for a board meeting in time to see the overnight results.
23:40Look at this one.
23:42Even the uninitiated, no offence Stuart, can see that there's a big difference.
23:51Yeah.
23:52That is fantastic.
23:53Yeah.
23:54Well done.
23:55Yeah, they sure are dead.
23:58Thank God for that.
24:00It's fantastic.
24:01And that's what now we can be absolutely confident that in anyone's hands, if you give these EDVs
24:09with the SIN, it'll work.
24:12The differences between scientific and financial concerns are set to divide the board.
24:18Tensions are mounting again over who should run the company.
24:21Unless we get proactive.
24:23Jesus Christ.
24:24Get proactive.
24:25Oh, get proactive.
24:27You know, this company shouldn't fail.
24:30That's just stupid.
24:31So if we can find a way of it not failing.
24:33We obviously need a solution by the end of the month.
24:36A scientist generally is regarded as somebody to be put aside after a certain length of time.
24:46And that the real business is in the business development people and the clinical trials
24:55coordinator, etc.
24:57It's a worldwide phenomenon and I don't understand it, frankly.
25:03It's just that money speaks and money is important.
25:08If we look back at why Jennifer and Amanchu have been so successful with this science,
25:13it is because they have been hands-on in terms of planning and executing experiments.
25:19And therefore, hardly anything ever goes wrong.
25:22When it comes to a business, you can't run a business that way.
25:27You cannot have a two-man band achieving a very high valuation from a buyer.
25:31And so therefore, they are going to have to learn to delegate and learn to let go a little bit
25:37in areas where they would probably feel more comfortable if they were, you know, far more hands-on still.
25:42You can't just say, OK, science is finished.
25:45Commerce is in now.
25:47You guys just go and make sure our patents are OK.
25:50It's not going to work.
25:52Would we lose freedom to operate here?
25:54No.
25:55If we were successful in human trials and then unsuccessful in, from a personal view, from an investment perspective,
26:00but also from getting a product to market, it would be a tragedy, a tragedy.
26:06And so that is my biggest fear because, arguably, it is within our control.
26:18We have dosed eight people, I think, with over 70 doses.
26:23And we've shown that a biological like this, derived from bacteria, is not going to cause any ill effects in people at the levels we're dosing.
26:34And probably at therapeutic levels, it's going to be safer than any chemotherapeutic that people get now.
26:41Whilst the downside of publishing leaves one vulnerable to copycatting, the upside for Jennifer and Himanchu has been the arrival of a nuclear scientist, Professor Dale Bailey.
26:53He read of their work in nature biotechnology and believed that he had an imaging process that could follow the EDV's passage through the body and into the brain.
27:06Today, the team of nuclear scientists and vets are combining with the ENGENIC team in a world-first experiment to prove the EDV can target a tumour in the brain.
27:21Images we're looking at on the screen here are the first dog that we've studied with this technique.
27:27What we're trying to do is to see where the mini-cells are actually going in the body.
27:32And so you can see in this combined image that we've got the tumour seen in the MRI scan, but that's exactly where the mini-cells are targeting.
27:39So when this signal you can see here stands out at you and you suddenly see that you've actually got the mini-cells in the target, it's a very exciting time.
27:50The EDV has done the impossible and clearly entered the brain tumour.
27:57The results are staggering in many ways, but they are also what we expected to see because of the strengths of the ENGENIC delivery vehicle.
28:08Armed with successful trial results and a breakthrough brain experiment, the scientists now change gear to continue the pursuit of a pharmaceutical partner in America.
28:19Taxi!
28:28Downtown Manhattan is a long way from the lab.
28:31The next days are stacked full of meetings with venture capitalists, big pharma, clinicians and finally an important scientific ally.
28:40In another world on Long Island, Bruce Stillman is president of Coalspring Harbour, one of the most prestigious laboratories in the world.
28:57I went over, this was soon after the company started, and talked to Jennifer Machu and they explained some of their ideas.
29:06And I was very excited about the whole concept of what they were trying to do and particularly the novelty of it.
29:13As co-author of ENGENIC's publications in biotechnology, Stillman is very aware of scientific competition and its implications.
29:22Science moves very rapidly and a competing technology could come along overnight.
29:28And there's no guarantee that this will actually end up being an approved clinical product, even at this stage.
29:35You do clinical trials in very advanced cancer patients, and to try a new drug technology in patients that have effectively failed all current cancer treatments is not a good way to test whether your drug is going to work.
29:53But then you go and talk to the oncologists and the people treating these patients and they say, well, you know, we ethically can't not treat them with, quote, the standard of care, even though the standard of care may not work and has been clinically shown not to work.
30:09Unfit patients for their clinical trials, threats to their leadership and the ever present battle for funding makes commercialising science an uphill battle all the way.
30:20That guy yesterday said, I'm the emperor and you're the gladiators and I do that or that.
30:25Yeah, that's okay.
30:27Oh, okay. Good way to start a meeting. Thanks a lot.
30:31On Wall Street, Jennifer and Hamanchu are joined by Chairman Wardman Brown to pitch to venture capitalists.
30:38You have a process here that I don't know that anyone's really thought about, you know, but very clever.
30:43Yes.
30:44So the expectation is that this could be for the current investors, the final round of it?
30:49I'm confident that they'd be very interested.
30:57At this point, Ingenic has to find either a pharmaceutical or a financial partner with enough funds to invest in the huge cost of the next trials.
31:07In the biotech industry, even though big advances have been made in China and India, all roads still lead to America.
31:16Tomorrow, Stuart is off to pursue venture capitalists in San Francisco, while Jennifer and Hamanchu fly to Indianapolis to meet with a leading pharmaceutical company.
31:26Eli Lilly's chief medical officer, Tim Garnett, plays a critical role in selecting partnerships for the company.
31:35I think one of the challenges that face the industry at the moment is that drug development is taking longer, it's costing more money, and the threshold for getting drugs approved is getting higher and higher.
31:47I think increasingly big pharma companies are looking to small biotech as partners in the drug development process.
31:55Forming an alliance with a company at an early stage is a much more speculative investment, but obviously a much cheaper investment from the pharmaceutical perspective.
32:04Once a drug is in phase three, there's a pretty high chance that it's going to be successful and that it's going to get approved.
32:10So licensing a drug from a partner at that stage of development can be a tremendously expensive undertaking.
32:17And of course, once a drug has already got approval by a regulatory authority, then we're talking about deals that can be hundreds of millions or even billions of dollars.
32:25With such money at stake for pharmaceutical companies, secrecy is paramount, and the scientists meet behind closed doors.
32:34That was really, really good. I reckon that's one of the best sessions we've had.
32:39Yeah.
32:40Don't you?
32:41I think it was fantastic.
32:42And I think it's because we're into humans.
32:46But also, talk about unmet needs. They've got a whole bunch of things happening that they need a resolution to.
32:53The next stop for Jennifer in Hemantua is Washington to meet with their patent attorney, Stephen Bent.
32:59They're preparing for a meeting with the FDA.
33:02They'll run it right through again.
33:04I mean, to some extent, it's a race to the patent office, I suppose.
33:08Many patent systems in the world are, in fact, first to file systems.
33:12Meaning that the person who gets the application that's effective, a good application on file, will be the patentee.
33:20The American Federal Drug Authority is one of the most rigorous drug regulators in the world.
33:27Jennifer and Hemantua have been answering their examiners for many months.
33:31I came to like them very much because they had a certain integrity, I guess.
33:37They were, by far, more concerned about the humanitarian aspect of it because they wanted to get this technology up and running so they could save lives.
33:47So they were brilliant people with good souls and that's not all that common in my business.
33:53Today is their first opportunity to meet the examiner face to face.
33:58Without FDA approval, the EDV cannot proceed.
34:03When they go to a pharmaceutical presentation and are able to speak about what they know best, which is the science and the potential of this technology, there's nobody any better than them.
34:15That's why the people who are often the best determinants of what will actually work are the people who came up with the invention.
34:20They know their own science better than anybody else. They will be the best salesperson for it.
34:26After a positive initial meeting with the FDA, Jennifer and Hemantua now focus on a potential clinical trial in Baltimore.
34:33Johns Hopkins is arguably one of the best trial venues in the world and their association with Ingenic will impress both U.S. farmers and the FDA.
34:44Long distance discussions have already begun about the possibility of a brain trial using the EDVs.
34:51We have a very large neuro-oncology center here and all we do are brain tumors.
34:55In a year we do between 800 and 900 craniotomies, so brain tumor operations for tumors, and that's all comers.
35:03The system is set up so that we treat a very large number of patients with brain tumors and the consequence to that,
35:10it's relatively straightforward for us to test therapeutics in a very systematic and rigorous scientific fashion to figure out if they're beneficial for patient care.
35:19This is the first time we are actually able to do live imaging in such a large animal to detect many cells in the tumor tissue.
35:28The potential of actually delivering radioactivity to a brain tumor, not to anywhere else, is there with this.
35:36Now you can see where the blood-brain barrier is intact. There's no sign of many cells at all.
35:42The white mass is where the tumor is and right in the middle of it you can see the many cells light up.
35:48Neurosurgeon Gary Gilear is keen to introduce the Hopkins superstars, leading brain authority Henry Brem and the trial supremo Skip Grossman.
35:59In 1984 when I came to Hopkins there was a 20 year period of no drug being approved by the EDVs.
36:05It's a generation, it's a lifetime that the FDA had not approved anything.
36:08Now when you speak to the FDA it's because nothing was presented to them in fashion that they could approve it because there was no data that met the criterion.
36:17We have a 16, 15 different brain tumor centers around the country that are all on board for us doing phase one, phase two trials. We've opened over 60 trials.
36:30The realization that we can actually move forward in a clinical trial arena is very, very exciting for me.
36:36I think their technology is very novel, is scientifically very solid and I think has a very high chance of working.
36:45Our view was that it will be a focused group here at Hopkins.
36:49When I see a patient in the office and I know that I have to have a discussion with them that despite maximal therapy at this point in time with surgery and chemotherapy and radiation therapy that the median survival is just over a year for them.
37:03I think the opportunity to actually test something that may change that for future generations is very stimulating for me and I look forward to this collaboration.
37:14Every meeting has been successful from our point of view.
37:18There is nothing that meets face to face communication.
37:21And Johns Hopkins meeting was spectacular. I think we learnt a lot as well.
37:26The Johns Hopkins team is clearly interested in trialing the EDV for the brain.
37:31However, Ingenic has to fund the trial at a minimum cost of $5 million and it can't proceed without regulatory permission from the FDA.
37:40As soon as they touch down in Sydney, they meet Stuart to present the results of their trip to the board.
37:50Although meetings in America have been positive, no US pharmaceutical company has yet stepped up to the plate.
37:57We quite simply cannot start the brain cancer trial without sufficient funds.
38:04So we can't start that trial without raising $15 million rather than $5 million.
38:10However, with financial stress on all fronts, the board is forced to raise interim funds to keep the company afloat.
38:17We've been directing our efforts more towards Asia.
38:23And we are making reasonable progress, but it's slow progress.
38:28And, you know, every month that goes by for Ingenic uses up roughly another half a million dollars.
38:38Yeah, it's pretty tough at the moment. Absolutely.
38:40We will run out of cash in probably two months' time.
38:47What we as a board then have to do is really focus the resources on what we must achieve in the next nine months
38:57to give ourselves the best possible chance of getting a partner across the line.
39:03After much debate, the board decides that their best option is to raise five of the $15 million with a new share issue to their original investors.
39:13In blue are people who like us. So far I've only found two.
39:22I'm finding it very stressful at the moment because we are back in fundraising mode.
39:28The deals that we're working on, as usual, won't overlap when we run out of money.
39:36So we've got to find some funds, at least for the interim period.
39:42Emotionally, it is very draining because we don't have the resources.
39:47We're just about 30 people.
39:49And we're constantly being asked, why haven't you commercialised everything?
39:52Why haven't you made your billion dollars? What billion dollars?
39:55There's nothing really that we ever disagree on as far as strategy or way to proceed or who to talk to.
40:03Right now we'd talk to Attila the Hun if he came in with some money, so...
40:07In the middle of all this, Stephen Bent, the company's patent attorney, arrives from the US with another set of concerns.
40:19Everything is converging on a point. Nobody's pulling in one direction.
40:23And for a small Australian company to have to pull that weight is asking an awful lot.
40:29That's why I'm trying to tell you that what's happening right now within Genic is absolutely critical
40:34because it's at this point where IP stuff and regulatory stuff, the wheels come off in many companies and they go belly up.
40:41If we were to lose the umbrella patent argument, would we lose freedom to operate in the US?
40:47No. You're not doing anything that would infringe those claims.
40:50Are there places where you can make errors? Yeah, yeah, just about every place, actually.
40:54And that's part of the problem and part of the challenge, that they have to really make all the decisions correctly
41:02because, unfortunately, at this point in the game, wrong decisions could be fatal.
41:08You're working with the right group, you're getting federal support so that you're not taking on that risk in toto.
41:14These are the things that can make or break a company.
41:20For Macho and Jennifer, I think one of the things that has come home to them is that their science, which is top notch, will not serve.
41:28It is not enough. It's not even half enough.
41:32The old song, you know, if you build a better moral strap, the world will come to you.
41:36That's all baloney. That's not true.
41:38You don't need great science to succeed. You do need great management to succeed.
41:44You cannot make it without it. One will not carry the other.
41:48Stephen Bent leaves two days later, wondering if his cautions have been heard.
41:54Unfortunately, there are other worries as well. The fundraising from the original investors has only bought in three of the $5 million they need for the Hopkins trial.
42:06It's only at the last minute their major investor champ Ventures comes to the rescue.
42:11And partly that's what I'm thinking. If we can catch up and say, you know, we're in for two, you know, we now need to wrap up this part of the round because then we're going to go quiet for a while.
42:23It does take a weight off our shoulders.
42:26So it gives us a time to potentially bring in a farmer deal and then hopefully after that we won't have to do any further fundraising.
42:39With $5 million in the bank, Jennifer and Amancha return to the U.S. to search for the additional funds they will need to start the brain trial.
42:53New York proves to be anything but bright lights. Biotech investment has completely stalled.
43:00A bleak economic forecast means Nginx potential deal partners have been unable to raise their own funds.
43:08Yes, it does take a long time to get something up and running.
43:12Although Jennifer and Amancha work day and night, it seems night has fallen on U.S. investment, particularly for offshore companies.
43:22In this market, only 0.4% of companies like Nginx are making it to market and many scientific innovations are being lost.
43:34Meanwhile, the World Health Organization confirms that cancer is the world's leading cause of death and predicts 22 million deaths to cancer between 2012 and 2030.
43:48This silent pandemic is set to overwhelm public health systems.
43:55Back at home base after an unsuccessful fundraising trip, Amancha's health buckles and he's ordered to take two weeks complete rest.
44:07Preparations for the second FDA meeting carry on without him.
44:15How's Amancha doing?
44:17Yeah, he's good, thanks. He's coming good, feeling better.
44:20Do you think it's important to have Johns Hopkins represented there?
44:24Yes.
44:25The FDA are the gods of all things medicinal in the U.S. and you have to run the gauntlet there to put anything into a human.
44:40Days later, Jennifer is back on a plane to the FDA meeting in Washington with board member Bob Graham standing in for Amancha.
44:50By the time they return, Amancha is back on deck and anxiously awaits their report.
44:56You can't have much better endorsement of what we're doing.
44:59Everyone we went to could see that this technology had enormous power and that we've already crossed the hurdles to show that it is a therapeutically feasible technology in humans.
45:12If we can show any hint of efficacy, whether that's target engagement or real efficacy, I think we're really home and hosed.
45:20I do believe in ingenious potential, I still wouldn't be on the board.
45:30You can't help but feel disappointed about where we are.
45:38Yeah, clearly the expectation was that we would be further ahead in terms of commercial success.
45:50Ingenic at the moment is in what is commonly called the biotech valley of death, which is depressing, and you have to get over the chasm and it's starting to cost a lot.
46:07There is an intensifying funding crisis and critics are gathering.
46:13There are a couple of ways to go.
46:15One is actually to seek to sell the company or to sell the IP to somebody pretty quickly to get it out there.
46:28The other is that the company will, regrettably, there is a prospect of some kind of administration if they can't get the money.
46:40I've had sleepless nights and I'm sure Hermantiu has too, but we haven't got the luxury to be scared.
46:46And we've got enough people around the place dropping their decks and, you know, and saying, oh, we'll all be ruined.
46:54We can't afford it because we've got a lot of mouths to feed and we've got a bigger purpose.
46:59Obviously there is the scenario we're trying to avoid, which is for the company to fall over.
47:09But then some snippet of the technology or a piece of data comes through and you think, we've just got to find a way around this because, you know, it's every bit as exciting as it was 11 years ago.
47:21It's arguably more exciting because we've got more tangible data. It's no longer just a dream. We need to make sure it doesn't end up being a nightmare.
47:32Frustrations run high as the scientists leave yet again for America.
47:37It's a whistle stop tour, that's for sure. We're going to San Francisco where we've got a couple of meetings, Boston, New York.
47:47This US trip finally yields a big fish.
47:52I couldn't help being attracted to NGINIC when I met Jennifer and Hemantiu. Their dedication, their devotion, their commitment, their energy comes burning through.
48:05Merv Turner has been the licensing manager for Merck, one of the world's biggest pharmaceutical companies, for 30 years.
48:12He's come to Sydney because he likes this science.
48:15And I really thought they had a tremendously novel and interesting idea. It really challenged a lot of the orthodoxes in our business and that made it interesting to me.
48:30And generally speaking, the big breakthroughs that you see come from unorthodox approaches.
48:36To us, he is a heavy hitter who totally believes in the technology and he has commercial savvy.
48:43How frequently do you take the scans?
48:46Every six weeks. Good boy!
48:49The NGINIC approach uses so-called bacterial mini-cells, small fragments of bacteria.
48:56It's generally assumed that administering bacterial fragments to patients is a bad idea.
49:05Those bacterial fragments, they're loading with drug.
49:08That is something that no one has attempted before or people thought possible before.
49:16So that flies in the face of conventional wisdom.
49:19They're assuming that those bacterial fragments loaded with drug can now be targeted to tumours.
49:26People have not done that before.
49:28Those particles would be considered by conventional wisdom too large to be transported across blood vessels to the site of the tumour.
49:39We had the first seizures in December.
49:41So when you put all these uncertainties together, you can see the kind of cliff that they have to climb in order to gain the confidence of investors and gain the confidence of clinicians, gain the confidence of regulators in their ideas.
49:58One of the areas in which I operate on is adrenal cancer and it's one of the most lethal cancers known to man.
50:09Unfortunately for people who have this cancer, they're generally young.
50:13Last one, then let Charlie do it.
50:15The more I've worked with them and the more I've looked at what other people around the world have to offer in terms of nanoparticle delivery, we realise that they really are on something special.
50:26Stan Sidhu's belief in the EDV delivers the team their biggest challenge yet when he clears one of his patients for compassionate use.
50:36A young woman of 27, she has been told that she has three days to live.
50:42We're hand making every single dose because no one's ever done this sort of thing before.
50:48It's exciting, sobering and it's scary.
50:52You can't help but get emotionally involved with the poor little thing lying there at, you know, mid-twenties with a whole life ahead of her and no life ahead of her at the same time.
51:04We're building platforms and then the next stage is to stabilise her, which we believe we've done and then the next stage after that is to cure her.
51:17This patient was 26 years of age, ovaries, uterus, everything resected. It was a pretty horrific situation.
51:24Hamanchu meets with Ian Fraser to discuss these remarkable results.
51:30The patient was already in palliative care, on morphine and the day when we actually came in with the first dose, we even had the priest standing there with a cross.
51:40We started and we cleared 13 weeks with clinically stable disease.
51:47We delivered 25 doses in 13 weeks in this patient.
51:51And most interestingly, the tumours were responding. Most of the metastases, they had stopped growing.
51:59This was the independent oncologist view, the patients not being hurt at all.
52:04And the disease is in clinically stable condition.
52:09I'm very impressed, I have to say. It's come a long way since I last spoke with you.
52:13Yeah, it has. The only thing is the patient was very heavy on morphine and the addiction really got bad.
52:19At which stage the patient decided, I just don't want to do anything.
52:23And enough of it.
52:24Yeah, so therefore we lost that.
52:27You have a patient who is days away from death.
52:29That's where almost virtually all cancer patients eventually end up.
52:36And that's when we currently say that, no, hope you pass away in peace.
52:44No, we are not saying that anymore.
52:47We strongly now believe that to the last day, if there is a will to fight, there is a way to fight.
52:55And this fight can be successful.
52:59And I am going to die.
53:02Right now.
53:03The quality of life forever forever can be discovered for a while.
53:08Yeah.
53:10And that's when we are focused.
53:12And the importance ofimmung andícia just do decks.
53:18Just like me properly or playing anyway.
53:21I'm so sorry to see why.
53:22And this is a way of fighting.
53:24You� can bardzo любим.
53:25I'm so sorry to know in a fight.
Be the first to comment
Add your comment