Hi Matthew, thanks for engaging and for your thoughtful comments/questions.
In non-pandemic times, yes. Australia has less requirements for a IND-type submission (GMP certificate only needed prior to enrollment, not at submission); you only need the HREC approval (IRB equivalent) and no national regulatory approval (just a rubber stamp); and depending on the indication and competitive pressures you usually get faster enrollment.
Agreed. I was talking more about regulatory speed to get into FIH.
You can still get a pre-IND meeting with US regulators and get their feedback before or in parallel to conducting a AU P1 (I recommend before, but if there are few/no uncertainties you might consider in parallel). So you don't have to choose. Agreed that FDA has requirements for foreign data, but it is a low bar (GCP, IRBs, ICs), and you could still get a majority of your data from outside the US. Rule of thumb is you need 20% of your data for an NDA/BLA to be from US populations, but even that rule has been broken successfully.
These are great points, I don't have a lot of experience with NDA/BLA submissions to foreign countries so your insights are valuable. I'll just note I was specifying people use Australia for P1. Agree that P2s and P3s are another ballgame.
As an ex-Alvean and also 15-year industry veteran I can maybe weigh in, particularly because I think this ties in to what was Alvea's main value proposition: speed for pandemic response. There were some aspects that enabled Alvea to go faster than a "from-scratch", hypothetical vaccine program: Alvea based its DNA-Omicron vaccine on an existing, approved vaccine platform (ZyCoV-D), and applied to SAPHRA instead of FDA/EMA.
But even trying to account for that, Alvea went faster than any company I'd seen that wasn't in early COVID pandemic-speed (with the full weight of mid/large pharma, funders, governments, regulators, plus also having based their vaccines on their own existing coronavirus platforms as opposed to someone else's). I'm sure there are instances of groups going faster (colleagues did an exhaustive ct.gov search and found them) but I still think its notable that a mostly inexperienced team was in the ~0.1% of fastest programs developed in the last 35 years. I attribute this to:
More sophisticated/aggressive risk appetite - Most biotechs are extremely risk averse, often to the point of irrationality. Execs might add months/years to their timeline (and spend $$$) to reduce risk by a tiny percentage since that is what they are optimizing. E.g. more US biotechs should be executing Phase 1s in the Australia (fastest option, cheaper, very safe bet) vs US (safest bet).
First principles thinking - As Kyle referenced, not listening to "conventional wisdom", always expanding the space of possibilities and stress-testing assumptions (probably assisted by seeing ourselves as "outsiders") was critical. E.g. nobody thought Alvea could source a comparator vaccine for its trial, the team was able to be one of the few orgs to achieve this.
Operational excellence - At least biotechs (I'm not as familiar with big pharma, but they are a different reference class) have a pretty sufficing perspective on timelines, Alvea had a maximizing approach: existing timelines were almost never satisfactory. Most companies would have stopped calling manufacturers after the first 3-5 vendors had similar timeline estimates, but at Alvea they would be exhaustive in their search to find a timeline that matched the targets. See Max's post for more details on all all these points btw.
Value alignment - Most biotechs/pharma are not staffed by many people who believe in the mission to the degree that Alveans believed in their mission. This improved coordination, reduced politics and increased personal risk-taking, e.g. picking a smaller, nimbler CRO versus a "nobody gets fired for picking IBM"-type CRO. This belief in the mission also contributed to the operational excellence - you will move faster if you think you are practicing for responding to the GCBR than if you are advancing a dermatology asset for stockholders.
For further evidence on the speed improvement: As part of the pivot towards a partnership/service-based business model that Kyle alluded to, we also conducted pilots that allowed us to analyze other biotech's development paths and were consistently able to save (on paper at least) 12-15 months off their timelines by applying lessons learned.
It is also important to note that from my perspective this product development speed focus did not contribute to the failure of Alvea, but I wasn't involved in the preclinical decision-making and the case could be made that jumping from one program to the next too quickly and without proper strategic consideration might have contributed (as Kyle also referenced above). Given all this, I would end by suggesting people run, not walk, to work with ex-Alveans (myself excluded).
We decided to close the project in 2022 for two main reasons:
We looked at engagement metrics and calculated how much throughput of volunteers and projects we would need to achieve a take-off trajectory on this metaproject and concluded it would take much active effort, partnerships and acceptance of the wider EA community. Given that this was a volunteer project we thought the odds of this happening were low.
CEA also communicated with us that they were considering including something similar in the forum. They ended up decided against it at the time (focusing on individual profiles more so founders could find each other), but in the meantime our volunteers became demotivated.
We also found many difficulties around project vetting, volunteer management and upkeep that made it a hard initiative to continue. Many of us still strongly believe more entrepreneurship within the EA community would be beneficial and that something like this metaproject would be very helpful. I am eager to discuss new metaprojects like this with anyone that wants to try to launch one and to communicate further leassons learned.
Great initiative. Whoever ends up in this role, we at impactcolabs.com would love to connect as we could both help identify potential candidates as well as help identify needs within EA orgs. We find that many EA orgs have volunteer needs that might be best served by a PA-type FTE. We will hopefully share more about these findings and the status of our 2.0 platform soon.
This is a great initiative! I help run Impact CoLabs that hosts many organization and projects in need of different types of expertise, tech expertise being a very common one. If you ever have free time, please reach out at [email protected] as we can connect you with high-impact projects in need. We welcome you (and anyone else) to also fill out a volunteer profile so organizations can find you directly as well. Thanks again for doing this with you free time!
Thank you for the feedback! You found a blindspot that most of us at Impact CoLabs and those we asked to review this post had, namely that we all had a concept in our mind for what a project platform was. I have adjusted the snapshot to hopefully aid in explaining the concept in general, but please let me know if this still doesn't address your issue.
Thank you for the kind words and the great feedback! You make a great point about 'volunteering', we will discuss that internally. I'm generally in agreement with your comments but would love to explore some of the nuance! Look forward to hearing form you, if you reach out and don't hear back, please message me here to make sure we are being responsive.
Hi Denis, thank you for your message and your offer to contribute, it is welcome. Since we are just starting out we still haven't built all the capabilities we have envisioned. For example, and as mentioned above, we were planning a list of tractable problems and project ideas to guide potential project leaders, as well as a list of past/failed projects or lessons learned from projects to ensure the community as a whole is not just spinning its wheels (e.g. this metaproject has had similar iterations in the past..). But your idea for a wiki that not only provides problem areas and project ideas but also provides thought-through analyses, roadmaps, required skills lists, available resources and community input is a huge improvement over our current plan. So I don't think the issue of not having project leaders identified upfront would be a critical problem, as long as you're OK with your wiki being separate from the project database. Ideally entrepreneurial EAs will find your project write-ups on Impact CoLabs and then create a project from it (or people that are screened from the platform due to low-impact ideas can be directed to those pre-vetted ideas).
We definitely want the ultimate version of Impact CoLabs to be the central node for project creation, and we want the resources we provide to reflect that. The goal is to be a more high-volume/low-touch, top-of-the-funnel solution than the incubators/accelerators like Charity Entrepreneurship or other upcoming startup factories. But even if we are not going to shepherd projects personally and diligently, it doesn't mean we can't try to provide as detailed and well-researched guidance as possible.
My only slight hesitation for your approach is the effort involved in development and upkeep, we would rather offer a lower-value solution (just a list of ideas) that we can guarantee can be maintained than a higher-value solution (detailed wiki with required fields for each project idea) that has a large chance of being abandoned after a while. So it all depends on volunteer interest in contributing and/or how we set it up. Would love to chat about this more. If you want to take this offline we would recommend filling out our new team member form so we can get you more background info on the project, or alternatively you can just email [email protected].
A group of us developed coviddash.org which was referenced in the NYTimes and had about ~30K visitors, directing between 10K-20K to vaccine trial screening websites or to the sites themselves. We had sites thank us for patients so we know we our counterfactual impact on trial enrollment was >0, but we are not sure of the total number we actually directed. If we accelerated just one vaccine for just one day though we probably helped save a few hundred lives. We were not funded by any EA org but some of us are EA-aligned.
I plan to write a more detailed recap/analysis on this and to discuss accelerating vaccine R&D during pandemics but haven't gotten to it yet because I already moved onto the next project...
Thanks Jan! Yes, we even reference your post in our detailed write-up and agree that vetting will be critical and a bottle-neck to maximum positive impact, particularly related to x-risk. Currently we have implemented a plan that we believe is manageable exclusively by a small group of volunteers, and have included a step in the process that involves CEA's Community Health team. Having said that, we don't think that is an ideal stopping point, we hope to expand into other forms of vetting pending general interest in the project, vetting volunteer interest and the building of other functionality or establishment of partnership with outside orgs. You can read more in sections IV.9 and VI.11 of the write-up about our thinking on these topics. Lastly, given your fantastic analysis in the past, if you would like to help out we would welcome any new team members that are interested in or familiar with this metaproject -- you can email [email protected] anytime!
Hi Matthew, thanks for engaging and for your thoughtful comments/questions.
As an ex-Alvean and also 15-year industry veteran I can maybe weigh in, particularly because I think this ties in to what was Alvea's main value proposition: speed for pandemic response. There were some aspects that enabled Alvea to go faster than a "from-scratch", hypothetical vaccine program: Alvea based its DNA-Omicron vaccine on an existing, approved vaccine platform (ZyCoV-D), and applied to SAPHRA instead of FDA/EMA.
But even trying to account for that, Alvea went faster than any company I'd seen that wasn't in early COVID pandemic-speed (with the full weight of mid/large pharma, funders, governments, regulators, plus also having based their vaccines on their own existing coronavirus platforms as opposed to someone else's). I'm sure there are instances of groups going faster (colleagues did an exhaustive ct.gov search and found them) but I still think its notable that a mostly inexperienced team was in the ~0.1% of fastest programs developed in the last 35 years. I attribute this to:
For further evidence on the speed improvement: As part of the pivot towards a partnership/service-based business model that Kyle alluded to, we also conducted pilots that allowed us to analyze other biotech's development paths and were consistently able to save (on paper at least) 12-15 months off their timelines by applying lessons learned.
It is also important to note that from my perspective this product development speed focus did not contribute to the failure of Alvea, but I wasn't involved in the preclinical decision-making and the case could be made that jumping from one program to the next too quickly and without proper strategic consideration might have contributed (as Kyle also referenced above). Given all this, I would end by suggesting people run, not walk, to work with ex-Alveans (myself excluded).
Just a quick update on this project (8 Oct 2023):
We decided to close the project in 2022 for two main reasons:
We also found many difficulties around project vetting, volunteer management and upkeep that made it a hard initiative to continue. Many of us still strongly believe more entrepreneurship within the EA community would be beneficial and that something like this metaproject would be very helpful. I am eager to discuss new metaprojects like this with anyone that wants to try to launch one and to communicate further leassons learned.
Great initiative. Whoever ends up in this role, we at impactcolabs.com would love to connect as we could both help identify potential candidates as well as help identify needs within EA orgs. We find that many EA orgs have volunteer needs that might be best served by a PA-type FTE. We will hopefully share more about these findings and the status of our 2.0 platform soon.
This is a great initiative! I help run Impact CoLabs that hosts many organization and projects in need of different types of expertise, tech expertise being a very common one. If you ever have free time, please reach out at [email protected] as we can connect you with high-impact projects in need. We welcome you (and anyone else) to also fill out a volunteer profile so organizations can find you directly as well. Thanks again for doing this with you free time!
Thank you for the feedback! You found a blindspot that most of us at Impact CoLabs and those we asked to review this post had, namely that we all had a concept in our mind for what a project platform was. I have adjusted the snapshot to hopefully aid in explaining the concept in general, but please let me know if this still doesn't address your issue.
Thank you for the kind words and the great feedback! You make a great point about 'volunteering', we will discuss that internally. I'm generally in agreement with your comments but would love to explore some of the nuance! Look forward to hearing form you, if you reach out and don't hear back, please message me here to make sure we are being responsive.
Hi Denis, thank you for your message and your offer to contribute, it is welcome. Since we are just starting out we still haven't built all the capabilities we have envisioned. For example, and as mentioned above, we were planning a list of tractable problems and project ideas to guide potential project leaders, as well as a list of past/failed projects or lessons learned from projects to ensure the community as a whole is not just spinning its wheels (e.g. this metaproject has had similar iterations in the past..). But your idea for a wiki that not only provides problem areas and project ideas but also provides thought-through analyses, roadmaps, required skills lists, available resources and community input is a huge improvement over our current plan. So I don't think the issue of not having project leaders identified upfront would be a critical problem, as long as you're OK with your wiki being separate from the project database. Ideally entrepreneurial EAs will find your project write-ups on Impact CoLabs and then create a project from it (or people that are screened from the platform due to low-impact ideas can be directed to those pre-vetted ideas).
We definitely want the ultimate version of Impact CoLabs to be the central node for project creation, and we want the resources we provide to reflect that. The goal is to be a more high-volume/low-touch, top-of-the-funnel solution than the incubators/accelerators like Charity Entrepreneurship or other upcoming startup factories. But even if we are not going to shepherd projects personally and diligently, it doesn't mean we can't try to provide as detailed and well-researched guidance as possible.
My only slight hesitation for your approach is the effort involved in development and upkeep, we would rather offer a lower-value solution (just a list of ideas) that we can guarantee can be maintained than a higher-value solution (detailed wiki with required fields for each project idea) that has a large chance of being abandoned after a while. So it all depends on volunteer interest in contributing and/or how we set it up. Would love to chat about this more. If you want to take this offline we would recommend filling out our new team member form so we can get you more background info on the project, or alternatively you can just email [email protected].
A group of us developed coviddash.org which was referenced in the NYTimes and had about ~30K visitors, directing between 10K-20K to vaccine trial screening websites or to the sites themselves. We had sites thank us for patients so we know we our counterfactual impact on trial enrollment was >0, but we are not sure of the total number we actually directed. If we accelerated just one vaccine for just one day though we probably helped save a few hundred lives. We were not funded by any EA org but some of us are EA-aligned.
I plan to write a more detailed recap/analysis on this and to discuss accelerating vaccine R&D during pandemics but haven't gotten to it yet because I already moved onto the next project...
Thanks Jan! Yes, we even reference your post in our detailed write-up and agree that vetting will be critical and a bottle-neck to maximum positive impact, particularly related to x-risk. Currently we have implemented a plan that we believe is manageable exclusively by a small group of volunteers, and have included a step in the process that involves CEA's Community Health team. Having said that, we don't think that is an ideal stopping point, we hope to expand into other forms of vetting pending general interest in the project, vetting volunteer interest and the building of other functionality or establishment of partnership with outside orgs. You can read more in sections IV.9 and VI.11 of the write-up about our thinking on these topics. Lastly, given your fantastic analysis in the past, if you would like to help out we would welcome any new team members that are interested in or familiar with this metaproject -- you can email [email protected] anytime!