Thinking of starting a biotechnology venture, but you’re a tech generalist?
What you’ll need to get your feet wet in biotech
Today I thought we would diverge from our usual data-science heavy stories and focus more on how our agroceutical venture, EMSKE Phytochem began. Along the way, we’ll highlight what we feel the table-stakes are for participating in the biotech startup scene today, and how to think about entering this risk-fraught sector.
EMSKE’s identity and motivations are inextricably linked to the fact that we are based in Africa. This geographical reality applies to about half of our volunteer contributors. This means that when we think about surviving (quite literally when you think about it) the coronavirus period, we look at what resources lie around us to help manage through the pandemic.
If you’re reading this from Europe or the US, your primary and most reliable pandemic survival strategy is to hunker down for a year while waiting for vaccine trials to complete. Here though, Africa’s a little different. Vaccines are desired here too, yes. But as with COVID test units, they’ll arrive later here than in the northern hemisphere. And as an economy, we can’t afford for everyone to “hunker down” — at least not if we want to avoid widespread social unrest. So there is a natural motivation to look to the one thing that Africa has in spades — it’s ecology.
Then it should be clear why EMSKE looks to natural products for drug discovery — because it’s practically all we’ve got to work with on the continent.
The motivation is there, but what about what really matters — the means? Well, the core mechanism underlying our efforts was illustrated from our very first Medium post on the topic: Back in late March as COVID was starting to arrive on Kenya’s shores, I wanted to know what compounds had the best chance of keeping my wife and me safe. Antivirals like the HIV protease-inhibitor antiviral, Lopinavir, had been gaining attention in early coronavirus academic literature. Since the epidemic in China was still in full swing I reached out to old classmates in China who might have advanced access to pop literature on antivirals efficacy on coronavirus (literature that would be hard for me to google effectively if it was in Chinese). If any antivirals were showing good performance, then it ought to be fairly easy to purchase it here in Kenya since, unlike in the US or Europe, antiretrovirals like Lopinavir are commonly available over-the-counter in the local pharmacies.
To my initial dismay, the papers my classmates turned up were less promising for lopinavir. Rather they highlighted a couple of plant-derived compounds as some unexpectedly high-performing protease inhibitors —the orange-rind flavonoids hesperidin and diosmin. And so began the first Medium post of our series which has since chalked up thousands of viewers to date.
Artificial protease inhibitors abound for well-known viruses like HIV. But the assumption has always been that a protease inhibitor could only possibly be a synthesized, pharma chemist-developed small molecule drug.
Our venture’s very existence challenges this assumption with the question, “What if, just like with antibiotics, nature itself had been developing protease inhibitors over the millions of years of evolutionary pressure?” It’s well known to medicinal chemists that plants are engaged in an eons-long chemical warfare battle with bacteria. What if many plant species had evolved antivirals against viruses, whether those viruses had adapted themselves for a plant or mammalian infection? After all, in the case of plant viruses, the plants have an obvious selection pressure to come up with compounds to fight the plant viruses that threaten them.
And in the case of mammalian viruses, we know that plants want to attract mammals to consume their seeds and spread them (“seed-spreaders”); the better to improve the survival probability of the plant’s progeny. Plants’ primary way to attract animals is to cover their seed in glucose product, one we know more commonly as “fruit”. Plants also produce critical vitamins that animals need to survive. Therefore, who’s to say that plants haven’t also adapted themselves to produce compounds that help mammals fight off viruses? This would be a further response to selection pressure on plants to support seed-spreaders’ health and ensure the propagation of the plants’ genes.
Whatever the precise evolutionary mechanisms are that could be in play, we assert that there are likely to be some among the millions of compounds produced in nature that are natural protease inhibitors —i.e. just as potent and perhaps even more selective than your average 3rd generation HIV protease inhibitor. For COVID, our work focuses on performing in silico studies and backs them up with historical academic literature for in vitro protease inhibition against the previous decade’s coronavirus, SARS-CoV. We’re also preparing to work on other tropical viruses that employ proteases of a similar class — Dengue and Chikungunya.
For purposes of forming a biotech startup to explore these hypotheses, what kind of expertise is involved? After all, none of our earliest participants come from Life Sciences backgrounds. That really ought to be a deal-killer for getting a biotech startup off-and-running.
But the current pandemic has illustrated just how broken the world’s pandemic response ecosystem is. As patients, some of the largest pharma companies we believed we would rely on in case of a pandemic had actually already exited the business of antivirals discovery before this pandemic even began — because it’s not profitable for a large pharma company to engage in infectious disease drug discovery: Instead, big pharma companies are firmly in the business of discovering the ‘next Lipitor’ — i.e. a drug for chronic sufferers of a condition, the wealthier and higher volume the market of patients, the better. (I hear diabetes is high on that radar, as well as Alzheimer’s).
Don’t get me wrong — if I ever come down with Alzheimer’s in old age, I’ll be very happy those companies studied the condition. But by contrast, effective management of a pandemic means having as few patients as possible (or else effective pandemic management had simply failed) — and that presents just a tiny market if you’re expecting each patient to pay for the privilege of nipping a pandemic in the bud by getting themselves dosed with effective antivirals. This means when it comes to stemming pandemics, it’s up to smaller companies to take the plunge and find the worthwhile revenue model to support their efforts.
So what to do if you’re coming from a non-Life Sciences background and spy a pathway for being useful to an important public health outcome? The temptation is certainly all to great to say “not my fight” and put your head back in the sand. But rather than hiding behind a lack of qualification, the solution is simple: get the life sciences people on board with you. They’re the most important source of validation, or especially, invalidation that your venture needs to decide whether to advance or to cut losses quickly.
And that kind of recruitment is exactly what we’ve done. We’ve brought on-board advisors a Ph.D. protein crystallographer, former USAMRIID aerosolized infection expert, and two plant medicinal executives with advanced degrees in chemistry and medicine; we have supporters who are in silico assay experts and phytochemical med chemists, We even maintain correspondence with competitors who are of a similar bent as us (after all, we weren’t alone in our interpretation of the bioscience literature) because of their valuable perspective as veteran executives of publicly-traded pharmaceutical companies that they graciously share with us.
So if you’re considering starting a biotech company but are afraid to do so because you don’t have the experience, remember the story of this pandemic. Not only is it “OK” for you to go ahead and pursue your research to start such a company, but we all need you to do it. Because relying on the existing ecosystem just isn’t cutting it.
And if you’re still not convinced, take a look at this recent video interview of Steven Kirsch. If you ever come down with COVID and find yourself benefiting from a low-cost drug to treat it, he’s most likely going to be the reason you get your hands on that drug. Because he’s one of the very few sources of funding for clinical trials of existing drugs. What’s his credibility for doing that? In conventional thought, he really shouldn’t have any; Although he invented the optical mouse and invested in FrameMaker and in the Infoseek search engine at opportune times, from a life sciences credibility standpoint, we really ought to be ignoring him.
However, during the pandemic, and demonstrating the strict rationality he had clearly put to use during those early business successes, he’s assembled a panel of virologists to review grant applications for trials of existing, off-the-shelf drugs. That’s the sum totality of his credibility, and that’s precisely as much as he needs. He’s a rational person with the results to show for it.
So if you’re wondering how to dip into starting a biotech venture, then Be Like Steve. In a world that misapplies funding and resources in medicine, your and my long term health may depend on it.