PopVax Goes Clinical – by Soham Sankaran

Holy shit.

What a trip. What a fucking trip. What an insane fucking trip this has been.

I’ve waited 5 years to write down these phrases: On 31 August 2026, the primary two individuals every acquired a dose of PVX-001, our broadly-protective COVID-19 vaccine candidate designed to guard towards future variants of SARS-CoV-2 which will emerge, in a first-in-human Phase I medical trial in Melbourne, Australia (ACTRN12626000891325).

This trial, which can enroll a complete of 36 wholesome grownup volunteers, is meant to evaluate the security and tolerability of the vaccine candidate, whereas additionally offering early knowledge on the magnitude and breadth of the immune response it elicits towards a number of variants of SARS-CoV-2. As of 6 October 2026, we’ve enrolled and dosed 14 individuals assembly our screening standards, with no critical antagonistic occasions (SAEs) reported. Participant follow-up and security monitoring are ongoing.

This vaccine embodies PopVax’s full-stack philosophy of growing new medicines – we constructed it on our personal computational protein design pipeline, mRNA-encoded VLP show structure, fridge-stable lipid nanoparticle supply car primarily based on our novel ionizable lipid PVXL-150, and in-house manufacturing course of at our RNA Foundry in Hyderabad, all of which we’ve constructed from the bottom up over the previous 4.5 years. Once the Phase I trial is concluded, PVX-001 will probably be made open-source for others to construct on.

The begin of this trial is a vital step on PopVax’s path to fulfilling our Million Lives Mission: to develop novel vaccines and therapeutics over the following decade that save 1 million lives every year. Safety and immunogenicity knowledge on our mRNA-LNP platform will permit us to speed up the interpretation of our preclinical vaccine applications – together with a single-dose rabies vaccine, a multivalent HCV vaccine, an grownup & adolescent TB vaccine, and a Strep A vaccine, all probably first-in-class – into medical trials over the following 2 years.

I’ve waited 5 years to write down these phrases, from once I first examine AlphaFold 2 and realized that machine studying was the way forward for drugs – earlier than the corporate even existed, when it was simply the kernel of an thought in my thoughts, nonetheless pristine and never but popped open by the warmth of actuality.

I’ve waited 5 years to write down these phrases, from once I took an uncharacteristic run on my beloved Juhu seashore, alongside the ocean that’s echoed in my ear since I used to be born, drenching myself within the pouring rain on my birthday because the pandemic-cursed 2020 was washed away to disclose the virgin sands of 2021, and determined that one thing basic needed to change – in our response to infectious illnesses, in how we make new medicines, and within the route my life was going.

I’ve waited 5 years to write down these phrases, from when Harish Iyer on the Gates Foundation took a $100k guess on me – a pc scientist with a minimal biology background – that no one else thought was a good suggestion, 5 years from once I first spoke with Ethereum co-founder Vitalik Buterin and the group at his scientific capital allocation fund Balvi and satisfied them this was doable and price funding with the Shiba Inu memecoin cash with which he’d been entrusted with out his consent, 5 years from each Indian investor I spoke to politely telling me that I used to be embarking on a idiot’s errand.

And but, and but, and but – after I flew all the way in which to Australia, waited patiently as the primary participant was checked, waited for the appointed second to strike, and noticed the nurse push within the plunger – after I noticed one thing I’d made be injected right into a fellow human being for the primary time… I felt nothing. I felt numb to the international stage. I felt disconnected from actuality, as if time was flowing ahead with out me.

Phew. Let’s take a deep breath. What the hell is happening right here?

I began PopVax largely as a result of I didn’t see Indian corporations responding to the specter of new COVID-19 variants quick sufficient, and even in any respect – the primary COVID-19 vaccines shortly misplaced efficacy because the virus mutated. We didn’t have variant-updated boosters in India for years after the emergence of the Delta and Omicron variants, which collectively killed hundreds of thousands of my countrymen. From the start, we aimed to design vaccines resilient to viral mutation that may proceed to supply safety towards not the present dominant pressure on the time of manufacture, however even future variants but to come back.

For PVX-001, we turned to the virus-like particle (VLP) structure, utilized in vaccines corresponding to Gardasil (HPV) and R21 (malaria), which shows many copies of the protein immunogen on a ball-like self-assembling construction, inducing the clustering of B cell receptors on antibody-producing immune cells and eliciting a way more potent antibody response than the immunogen by itself. This clustering additionally typically induces a broader antibody response – one which is ready to neutralize a wider set of mutated variants of the pathogen.

The catch is that VLP vaccines are notoriously arduous to fabricate in vitro, with every immunogen variant you placed on the VLP demanding its personal painstaking cycle of optimization for the required situations to efficiently assemble and purify it after the person monomer subunits are produced in cells. Merck’s HPV vaccine Gardasil 9, for instance, takes as a lot as 4 years to fabricate from begin to end. That is simply too lengthy for a vaccine towards a virus that births a brand new dominant variant as quickly because the seasons change.

Enter RNA, which is produced by way of in vitro transcription (IVT), a synthesis course of carried out utilizing enzymes in a largely cell-free vogue, and purified with strategies that don’t change all that a lot from sequence to sequence. We produce mRNA in a ‘one-pot’ response that takes a single day, and our complete manufacturing course of takes per week, a far cry from the numerous months to years required for standard VLP vaccines produced right now.

PVX-001 is constructed round messenger RNA (mRNA) that instructs cells within the human physique to provide a designed protein that self-assembles inside the cell right into a VLP that shows an engineered model of the SARS-CoV-2 Receptor-Binding Domain (RBD). We flip the physique into the manufacturing unit for the VLP, and let it deal with the troublesome elements of the method, combining the manufacturing ease of RNA with the immunological efficiency of VLP show.

When utilized to the design of a wild-type COVID-19 vaccine, our RNA-encoded VLP method leads to a >50x enhance within the elicited neutralizing antibody (nAb) titer in mice in contrast with the identical dose of RNA encoding the identical immunogen as is, in addition to a >20x enhance in nAb titer in comparison with the identical dose of the mRNA sequence from a US FDA-approved first-generation wild-type COVID-19 vaccine.

While it’s straightforward to replace the mRNA sequence in our vaccine to focus on new variants with out altering the manufacturing course of, we could not want to take action as typically as present vaccines do – our wild-type SARS-CoV-2 RBD-based VLP show assemble was in a position to elicit potent neutralization titers towards the Gamma, Lambda, and Omicron BA.1 variants of SARS-CoV-2, whereas a US FDA-approved mRNA-based COVID-19 vaccine comparator sequence on the similar dose was not, demonstrating that the VLP immunogen show method leads to the elicitation of antibodies that neutralize a better breadth of variants.

We’ve now utilized this design method to a newer SARS-CoV-2 variant, which we’ve used as the premise for the model of PVX-001 that has now entered the Phase I medical trial. Our preclinical immunogenicity in mice is aggressive with that of mNEXSPIKE, Moderna’s much-improved second-generation vaccine. We hope that this vaccine would require fewer boosters and fewer frequent variant-specific updates to take care of its efficacy over time, even because the virus mutates quickly.

Being in a position to make the vaccine, nevertheless, solely solves half the issue – you additionally want to have the ability to transport it all around the international stage to the entire individuals who want it.

Our lipid nanoparticle (LNP) formulation, the important thing element that permits the mRNA to enter human cells, is predicated on our novel ionizable lipid PVXL-150. We’re notably pleased with the truth that vaccines utilizing this LNP formulation might be saved at 2-8 °C, common fridge temperatures, for no less than 9 months with out lyophilization (freeze-drying), slightly than the frozen -20 °C or ultracold -80 °C storage required by the first-generation mRNA vaccines accepted for COVID-19. This will permit for straightforward distribution throughout the international stage utilizing established refrigerated provide chains for medicines, making our vaccines easy to deploy at scale in growing nations.

Every dose of PVX-001 was constructed on the RNA Foundry, PopVax’s full-stack R&D lab and world Good Manufacturing Practices-aligned medical dose manufacturing facility in Hyderabad. Our computational researchers and protein designers sit simply toes away from experiments being performed by our scientists, who can gaze by way of the glass to observe the manufacturing course of in full swing. This permits for fast and seamless collaboration that considerably will increase the speed of our engine for translating AI into drugs. In slightly below 5000 sq. toes of GMP manufacturing area, the RNA Foundry can produce as much as 1 million doses of latest medicines every year, from plasmid DNA to formulated mRNA-LNP, together with testing each batch towards an in depth panel of analytical strategies we developed and operationalized at our on-site Quality Control lab. We even make our personal GMP-grade ionizable lipids right here!

Every dose of PVX-001 can also be the product of a world collaborative effort. Our work was initially seeded by the Gates Foundation, considerably funded by Vitalik Buterin’s Balvi fund, and was helped throughout the end line by an capital allocation from Meta co-founder Dustin Moskovitz and Cari Tuna’s Good Ventures, suggested by the nice of us at Coefficient Giving. The vaccine was a part of the US National Institute of Allergy and Infectious Diseases’ (NIAID) Project NextGen, which gave us entry to very important scientific and regulatory recommendation, and beneath which the doses we manufactured on the RNA Foundry in Hyderabad have been stuffed in vials at ABL in Rockville, Maryland. The trial was accepted by an Australian Human Research Ethics Committee run by Bellberry, and is being performed by Nucleus Network at their facility in Melbourne with help from Emerald Clinical.

Before reaching a participant, each single dose journeyed by way of 4 continents, from being manufactured in India and stuffed right into a vial within the United States to catching a flight by way of Germany to the trial website in Australia.

Once the Phase I trial of PVX-001 concludes, we’ll open-source the design and manufacturing data wanted for others to provide and construct on it, and we won’t implement any of our mental property rights towards anybody who makes use of it to make vaccines towards any betacoronavirus – the viral genus that features SARS-CoV-2, SARS-CoV, and MERS-CoV.

We are doing this as a result of SARS-CoV-2 and its shut cousins stay a considerable pandemic threat. In simply the previous few many years, they’ve induced one main epidemic (SARS), one shut name (MERS), and one world pandemic that killed hundreds of thousands. The designs developed after the unique SARS outbreak gave the primary era of COVID-19 vaccines an important head begin in 2020. We need humanity to have a good higher head begin subsequent time: a broadly-protective, refrigerator-stable vaccine that any scientist, vaccine producer, or member of the general public, situated anyplace, can enhance, adapt to their wants, and manufacture with out having to fret about IP.

We are additionally doing it due to what we noticed through the pandemic. The finest and most recent RNA vaccines have been largely unavailable to poorer nations, as wealthy nations secured the majority of the availability, and vaccine producers in nations like India by no means up to date their merchandise for Omicron and later variants. As Vitalik has argued in his writing on d/acc – defensive accelerationism – the potential to design, develop, and manufacture the following era of vaccines have to be globally distributed. An open-source vaccine, constructed on an mRNA-LNP platform that may use present medical provide chains in growing nations, is a concrete step in the direction of ensuring that the rising international stage in Asia, Africa, and South America is rarely once more left ready in the back of the queue.

PVX-001 is just the start. We’re growing six new vaccines, personalised most cancers medicines, and focused autoimmune therapies to satisfy our mission to save lots of 1 million lives every year. Sometimes I lie awake at night time and agonize over all of the screwups we’ve made – the botched experiments, the missed alternatives, all of the fumbles and stumbles that delayed us by a 12 months, or possibly even two, and I wonder if we are able to actually pull that off within the subsequent decade.

But now that we’ve traversed the thorny path from idea to clinic, we’ll mix our newfound data of tips on how to get one thing from perception to injection with our full-stack method to quickly speed up these new medicines in the direction of sufferers, with out compromising rigour or security. This would be the first of many first-in-human trials, every following ahead of the final, with rising rapidity till we’re translating new medicines to sufferers in weeks, not years.

I’m the prodigal son of two homoeopathic docs who don’t like vaccines very a lot, a lapsed laptop scientist who moved my Y Combinator-backed robotics software program firm from San Francisco to Pune on the peak of the pandemic, and a licensed madman who, on the recommendation of a high-schooler, turned down a number of time period sheets and shut down my software program startup to start out an AI-powered biotech firm with out realizing very a lot biology, in a pre-ChatGPT and Claude Code period when it wasn’t but clear that AI might do all that a lot biology, in a metropolis I’d by no means been to earlier than signing my lab lease, and in a rustic that doesn’t do – or fund – very a lot biotech R&D, the place many of the native pharmaceutical titans are engaged in a multi-generational sport of ‘the ground is lava’, wherein any capital allocation within the growth of latest medicines is the ground. Luckily, their personal jets hold their toes off the fast-heating floor.

With me up to now?

The charismatic and scarily energetic Nalam ‘Madhu’ Rao on the Centre for Cellular and Molecular Biology granted me 100 sq. toes of shared lab area in his incubator hours after I landed in Hyderabad in late 2021, nonetheless the quickest I’ve ever seen Indian academia transfer, I bankrupted myself shopping for lab gear, managed to recruit wonderful scientists who have been so bored at Indian generics and biosimilars corporations that they responded to a LinkedIn submit asking for ‘folks to make mRNA’, and satisfied Harish Iyer, a Gates Foundation officer who used to run the pioneering Indian vaccine firm Shantha Biotechnics, to present us a $100k contract for ‘public consciousness’ of world well being – that’s, the notice that somebody in India might make mRNA vaccines in any respect.

We couldn’t get our palms on DNA templates quick sufficient till Stanford’s Rhiju Das really helpful Twist Bioscience, however we needed to get a buddy in an SF lab to trans-ship them to us as a result of Twist didn’t but have India logistics arrange, and all of it took so lengthy! – so interminably lengthy! – till Suresh made the mRNA late one night time within the lab and, lo and behold, it labored, it expressed (yay!) in cells… however the LNPs didn’t fairly work in mice (boo!). So Sourav, our first worker, used a torture machine with a guide plunger again and again to squeeze out the invisible particles till they lastly received to the constant dimension they wanted to be. Meanwhile, Maunish, the son of one in every of my father’s closest colleagues, neither of whom I had seen for over a decade, turned out to be a star scholar of Pieter Cullis, one of many nice pioneers of lipid nanoparticles – on seeing that we had managed to get artificial mRNA to precise proteins in cells in India, Maunish went into some sort of rapturous trance wherein he determined to maneuver to Hyderabad and do science with us.

Experimental success bred sooner spending, which introduced our checking account near damaging territory as soon as extra. So, as typical, I wrote an indignant op-ed {that a} Thai gentleman preferred sufficient to attach me together with his good buddy who was inquisitive about COVID-19 – a superb buddy who turned out to be the uncommonly considerate and uncompromisingly moral Vitalik Buterin. We received improbable knowledge from our RNA-encoded VLP method, however once we tried to get another person to fabricate the vaccine, we realized it will be a lot too costly and would take too lengthy, so Thiru and Praveen helped design and construct a facility so compact our contractors instructed us it wasn’t buildable, solely to instantly face-

You get the thought.

The ultimate act of this frantic theatrical manufacturing performed out early this 12 months. We have been a part of NIAID’s Project NextGen, with the trial set to occur in Maryland, funded by the US authorities. Unfortunately, after the change of administration and attendant rearranging of priorities, we have been instructed that the trial wouldn’t go forward. In shock, we scrambled to maneuver the trial to Australia, discovering a website and a contract analysis group on the fly, with Darshit writing the docs for the ethics committee and Hannah working throughout two oceans to get the medical protocol locked down whereas we juggled the upkeep and cargo of the vaccine vials again from the US to an as-yet-unknown location.

No surprise I used to be numb.

And but, towards all odds, we persevered and prevailed. The vaccine firm that nobody thought was a good suggestion has grow to be a clinical-stage AI-powered biotech that’s beginning to hit its stride. A number of days after the primary injection, I stood by the ocean on Sydney’s Bondi Beach, I felt all of it sink in – each the joyous significance of what we’d simply completed, and the enormity of what’s but left to realize.

PopVax is accelerating to match the dimensions of our imaginative and prescient. From a standing begin, we’ve generated hundreds of thousands of candidate proteins utilizing frontier machine studying strategies and AI fashions, designed 1000+ novel lipids, screened over 5000 distinctive LNP formulations, injected over 1300 distinct vaccine constructs into animals, and performed 10s of 1000s of practical assays. Each experiment permits us to enhance our designs and raises the ceiling of what our medicines can do to assist folks in want.

We will take many, many photographs on aim – greater than could appear well-advised. More than are comfy for a spectator to ponder, even. We received’t win ’em all – life is stochastic – however we’ve made peace with that. Watch carefully, else the way forward for drugs will occur within the current with out you.

If what we do excites you, PopVax is hiring for a number of crucial roles in the mean time:

1. Principal Scientist – Analytical Method Development and Senior Scientist – HPLC Method Development: We design hundreds of thousands of latest molecules – proteins, RNA, LNPs, and extra. Your job is to determine tips on how to characterize them at high-throughput with out sacrificing rigour, repeatability, and robustness, in addition to to assist make these strategies GMP-grade as a part of the handover to QC. We intend to take new medicines into medical trials in weeks, not years, so we have to construct adaptable analytical platforms, not bespoke strategies that work for just one molecule. We strongly choose candidates with the power to write down code to construct automated knowledge evaluation pipelines for his or her strategies – LLM-generated code is ok so long as you’ll be able to comprehensively validate the logic and output of the pipelines.

2. Head of Quality Control – We manufacture our personal medical doses on the RNA Foundry, and each analytical methodology we develop for a brand new molecule finally has to grow to be a validated QC methodology. You’ll lead the group that assessments each batch to global GMP requirements, tackle methodology transfers from analytical growth, and construct a QC operate that may hold tempo with a pipeline aiming to achieve the clinic in weeks, not years.

3. Junior Scientist – Vaccine Immunology – Our vaccine applications halt or advance on the immunogenicity knowledge that comes again from animal and organoid research. You’ll run the assays that produce that knowledge – ELISAs, pseudovirus neutralization, and bacterial growth-inhibition assays – and coordinate animal research with our inner groups and CROs, following every research from plan to samples to consequence. We choose candidates who can write code for routine knowledge evaluation.

4. Head of Legal – Our first vaccine was manufactured in India, was stuffed into vials within the US, and has now entered a medical trial in Australia. We work with dozens of counterparties – funders, governments, universities, CROs, and suppliers – with extra added every week. You’ll personal the day-to-day of our Indian authorized work, from contracts to compliance to labour legislation, work with the authorized groups supporting our UK and Australian operations, and ensure paperwork is rarely the bottleneck between our new medicines and the clinic.

5. Chief of Staff to the Chief Science Officer: Our CSO wants a associate who can take experimental planning and coordination off his plate in order that he can spend extra time considering arduous about our thorniest issues. Your complicated scientific hypotheses into clear executable plans, coordinate with scientists to see every experiment by way of, and analyze the info to assist plan the following spherical of iteration. You’ll want a powerful scientific background, a pointy eye for element, and boundless power to maintain formidable scientific work shifting. To apply, electronic mail dhruv [at] popvax [dot] com with a human-written rationalization of why you’re one of the best individual for the job.

If none of those are a superb match, check out our jobs page or electronic mail us at work [at] popvax [dot] com.

I’m Soham Sankaran, the founder & CEO of PopVax. Feel free to electronic mail soham [at] popvax [dot] com when you’re inquisitive about discussing the challenges of quickly turning machine intelligence into medicines.

You can discover me on Twitter/X @sohamsankaran. You may also comply with PopVax on Twitter/X, LinkedIn, and YouTube, or electronic mail us at hiya [at] popvax [dot] com.