SoftBio - A Genie on the Verge of Escaping Its Bottle

It was the summer of 1986. Having just spent six weeks at the Meadowmount School of Music in bucolic Westport New York, I sat by the window in my desolate dorm room, straining to see any sign of approaching lights through the torrential downpour. My fellow musicians had left hours before. The only remaining faculty member was my dorm monitor, dutifully delaying her departure on my behalf. After an agonizingly long wait filled with bouts of wild speculation, I heard the faint sound of gravel crackling under an approaching vehicle. Though it was no surprise, indeed more like relief, to hear that my parents’ car had broken down, I wasn’t prepared for what I’d learn on the long drive back home – that my mother had been diagnosed with stage IV Non-Hodgkins Lymphoma and given six months to live.?

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In the following months, multiple rounds of chemotherapy, radiation, and a bone marrow transplant had little impact. My father, sister, and I began to learn the many things necessary to fill my mother’s shoes, preparing for what seemed inevitable. But an unexpected miracle arrived in the form of a Stage II clinical trial for alpha interferon, the first genetically engineered immunotherapy cancer drug, approved by the FDA earlier that year for treatment of hairy cell leukemia. Though alpha interferon’s physiological mechanism is still not entirely understood even today, it was observed to stimulate the immune system to identify cancer cells and slow their growth and migration. Indeed, within three months of starting a course of interferon injections, my mother was in remission, and has been cancer-free since. Surprisingly, however, the trial results were declared inconclusive - apparently not everyone in the study had fared as well.?

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Thirty-five years later, such is still the fate of clinical trials for 9 out of 10 experimental drugs. In fact, the number of annually approved drugs per billion dollars of industry-wide R&D has declined by 50% every 9 years since 1950 - a diseconomy of scale prosaically referred to as Eroom’s Law, an inverse form of Moore’s Law. However, after 7 decades, we’re finally witnessing the tides turn.?

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The most advanced treatment available today for certain late-stage lymphomas and leukemias is CAR-T immunotherapy, in which a patient’s immune cells are harvested, genetically modified to target specific surface proteins on cancer cells, replicated outside the body, and reinfused into the patient. Though currently costly, time-consuming, and exhibiting some serious side-effects, CAR-T’s efficacy in the clinic often surpasses that of conventional chemotherapy, yielding unprecedented remission rates for those who have exhausted all other treatments. New generations of the treatment are under development that aim to mitigate side effects and reduce costs, including in-vivo modification of a patient’s T-cells, adaptive cell targeting and even externally-controlled on/off switches, amongst other improvements.

Though alpha interferon now seems like a blunt tool compared CAR-T, both are fundamentally immunotherapies – ones that coax the human immune system into fighting a foreign body. Similarly, the Pfizer and Moderna Covid-19 vaccines (amongst others) are based on an mRNA-based technique that marshals our own cells (in this case without DNA modification) to manufacture the characteristic Covid ‘spike protein’ for presentation on their surfaces. Our immune system responds to these foreign agents by producing complementary antibodies, thereby conveying protection (or at least preparedness) against future Covid infection.

In both the CAR-T and mRNA techniques, human cells are essentially digitally reprogrammed, leveraging their intrinsic biological machinery to produce desired new behavior and function. Though such biological programming is broadly based on a scientific principal dating back to 1957 (the so-called central dogma of biology), turning this principal into practice is far more complex than the dogma suggests. Consider that even a single human cell is vastly more complicated than anything humanity has ever engineered. Understanding and manipulating biological systems requires us to reverse engineer (a.k.a discover) life’s inner workings, in contrast to computer engineering in which we have the luxury of defining the building blocks, operating systems, and programming abstractions that numerous industries have become reliant upon.

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Fortunately, the last two decades of multidisciplinary research has led to a rapid proliferation of biological sensor and synthesis (read/write) devices with performance / cost curves far outperforming Moore’s Law. The resulting ability to sequence a genome, selectively edit portions of it, and observe resulting changes in cellular function has given rise to rapidly growing data sets encoding deep insights into how biological systems operate. Recent advances in machine-learning techniques and cloud computing are helping to elucidate these insights from seemingly overwhelming quantities of data.

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Leveraging these insights, our currently rudimentary biological programming tools will evolve into foundational bioengineering platforms providing for replicable design, verification, synthesis, and real-time operation of biological ‘circuits’. Moreover, the biological circuit designs so enabled will be customized to the specific needs of the individual rather than the general populous, and thus will benefit from higher clinical success rates. Personalized drugs will become commonplace, akin to the role that application-specific integrated circuits (ASICs) play in the microelectronics sector.

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Innovation in computational design platforms for bioengineering, we term SoftBio, and offers an economic value proposition rooted in imbuing higher developmental predictability and clinical success rates to therapeutic or diagnostic assets, realizing the long-awaited transition from drug discovery to drug design.

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SoftBio’s raison d’être is to enable biotech to yield higher clinical success rates, progress more quickly and predictably, and to be accessible by a broader investor and entrepreneurial talent base.

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Companies that lead the SoftBio revolution will become as iconic as Cadence, Xilinx, Intel, Oracle, Microsoft, and Google. Though such industry transformation will unfold over decades, its seedlings will be planted this decade, offering new opportunities to invest in multi-disciplinary teams tackling hard problems with long-awaited disruptive economic impact in pharmaceuticals, diagnostics, and health-care services, let alone agriculture, cosmetics, construction and space exploration. Once the Genie escapes, no industry will remain untouched by the power of SoftBio. ?

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Given the platform-nature of SoftBio innovation, one can expect these investment opportunities to exhibit increasingly tech-like capital requirements and risk profiles, broadening the applicable investment ecosystem beyond traditional biotech venture firms.

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At Hyperplane, we invest in passionate and pragmatic entrepreneurs with ambitious visions of transforming foundational industries through technology-enabled automation. We seek economic inflection points in markets with unfulfilled latent demand and supply chains ripe for disruption, offering investment opportunities to reorganize industries around a new set of leaders. Healthcare and the life sciences exhibit these characteristics in spades, and SoftBio is one area of particular interest to us.

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This is the first part of a blog series that will explore the fundamental challenge facing the healthcare and life sciences industries today, the emerging technologies with promise to overcome it, alternative investment models to spur such innovation, and the characteristics we expect to see in startups aiming to become the iconic leaders of the SoftBio era. ?

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For those interested to read more, upcoming content will be oriented to an entrepreneurial community at the intersection of tech and biotech. As such, it assumes familiarity with language and fundamental concepts from both sectors, though an attempt is made where possible to provide embedded links to supporting material for a broader audience. Lastly, I apologize in advance for the academic style of the writing – my engineering background has trained me as such, and it’s hard to kick. Your feedback is not only welcome but solicited.

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Most importantly, if you are an entrepreneur interested in tackling the SoftBio challenge, we are keen to hear from you!

Naimish Patel is a Boston-based entrepreneur with operational, investing, and board experience in telecom networking, smart grid, enterprise software, and life sciences. Naimish was one of four founding team members of Sycamore Networks where he was the architect of Sycamore’s products from inception through IPO. Subsequently, Naimish founded Gridco Systems, a provider of intelligent power routing and regulation solutions, enabling electric utilities to reliably integrate renewable energy, serve electric vehicles and enhance system-wide energy efficiency. During this time, he served as board director for the Advanced Energy Economy, an association of businesses committed to secure, clean, and affordable energy, on behalf of which he delivered expert testimony before a Congressional committee on national energy security. Naimish is currently an investor with Hyperplane VC, a seed stage venture fund, serving as board director for portfolio companies in the telecom, IoT, and bioinformatics domains. ???