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Thoughts on interviewing with YC as a science based startup

TDLR; Applying to YC is an interesting experience, and have a clearer process than many VCs. I would recommend it, even for solo founders and science-based startups.

I applied to the YC winter 2019 batch. I viewed the whole process as relatively low probability. YC gets more than 5000 applications. Out to these ~500 get invited to interview onsite.

My idea was for a cheap simple device to read/write DNA. I’ve blogged about my approach before here and here, you can find the complete YC application below. While I wasn’t accepted, I interview with YC a pleasant and worthwhile experience. My hope is that this post will encourage other science based startups and solo founders to apply to YC.

My application was for an idea stage startup. I didn’t spend much time putting the application together, went for a walk to think thing over and then did a couple of takes to create the intro video:

As a solo founder, idea stage, science based startup I thought my chances were quite slim. I fired off the application anyway, as the investment of time on my part was relatively low.

You don’t need a deck, and the focus seems to be on the idea and the team. This is in contrast to most seed stage VCs (even accelerators) who require a deck and likely multiple meetings.

The other difference with YC is the timeline is very clear. Many VCs will keep you hanging, not reply, or ask you to check back in after some vaguely specified goal has been reached. It’s understandable, but can be painful.

YC reply on a fixed timeline [1]. This makes the whole process clearer to everybody involved. After putting in my application, I received an email a few days later requesting a phone screen.

The phone screen was about 10 minutes. Quite high level, and mostly just clarified the play, and how it fits into the DNA sequencing space (see the application below if your interested in further details [1]).

The deadline came and went, and I heard back the day after the official deadline that they’d like me to come to Mountain View to interview.

YC cover your travel expenses up to a limit. Coming from Japan, the travel budget was 1000USD and hotel budget 350USD.

The interview process itself was pretty painless. My interview panel consisted of 3 people. One had a background in Biotech and had in fact worked at a DNA sequencing startup.

The conversation was good, they were very focused. They didn’t focus too hard on the technical aspects of the play. After discussing the play and initial focus, we moved on to talk about how I would beat the current market leader (Illumina).

This wasn’t really the play, Illumina are very cheap on cost per base. But their cost per run is very high (500USD+). The idea was to focus on applications were a very low cost per run (10USD) would be beneficial, bootstraping on DIYBio and Synthetic Biology applications. My thesis is diagnostic instrumentation will likely require a cheap run cost… but throughput isn’t so critical for many applications.

But they wanted to see the Illumina-killer play worked though. This is not unreasonable. While this might not be the pitch, I think it’s reasonable that I should have the idea worked through… I guess that I have the “idea maze” fully explored.

In total the interview lasted about 15 minutes.

I heard back later that evening that I didn’t make it into this batch. They gave detailed feedback (which you’ll find at the end of this post [2]), again this is something you don’t receive with most VCs.

I was left feeling quite positive about YC. The process was very clear, and I think they can do a reasonable job of selecting and funding science heavy startups.

They’re quite unique in a number of aspects. The goal seems to be to create an efficient pipeline for selecting startups that can increase their valuation from a nominal 2MUSD to probably ~20MUSD in a 3 month timeline (and eventually growing to unicorn size).

After the 3 month period is up, you get put in front of a bunch of 2nd stage investors and the hope would be that you raise at this increased valuation.

500 startups are interviewed. From my experience I’d guess they spend <30 minutes evaluating each one. This isn’t enough time to do a deep dive, but it’s probably the point of diminishing returns. After this they have a strong enough signal, to filter 500 startups down to 100 which have a reasonable chance of moving forward.

This pipeline likely works as well for science based startups as traditional tech. And I know that in my batch a DNA sequencing startup was selected, and will be following it with interest.

As for me… I’ll probably put my startup on hold for now. The timing isn’t right for me to move to the US, and working on this idea would likely take more money than I have.

If you’re doing a science based startup in Japan, or I could conceivably help out remotely, please get in touch! (new at sgenomics dot org).

Notes

[1] The interview acceptance came about a day late. Given the volume of applications they have I find this more than acceptable.

[2]

I confirmed with YC that they are happy for me to share the feedback, so here it is!

Unfortunately, we’ve decided not to fund Opusone for the winter batch.
This was a close call for us. I was very impressed by your background in the space – we like to fund people who are deep technical experts and you certainly are. We also really like the general pitch of an “altair basic of genome sequencing”. If you’re not familiar with the term, there is a great essay Paul Graham wrote that I think fits very well with your core thesis.

We had two issues that gave us pause. One, it was just very early in terms of either building the device or seeing if a device this low-end would actually be interesting to DIY bio people. And two, it wasn’t clear to us how the device would go from low-end to taking over the mid-tail and eventually taking over the market.

Let me say a little more about the second issue. We’ve seen in past companies that it’s not inevitable that the low-end option ends up taking over the market. Sometimes it gets stuck as an educational tool, which tends to be a small market, as the high-end options continually drive costs down. If you’re pursuing a “altair basic becomes microsoft” strategy, you want to make sure that you have a clear technical path where you can start with a low-accuracy device but keep improving the accuracy until you have something that is competitive with Illumina but less expensive. YC companies like Airbnb and Stripe have done this basic strategy really effectively.

I think you’re onto something here and I’d strongly encourage you to keep working on it and re-apply to YC in March for the June-August batch when you have developed the idea more. If I can be helpful in the meantime, please let me know.

Thanks very much for flying out here from Japan to meet with us. I enjoyed meeting you and hope you’ll keep in touch.

[3]

Application:

COMPANY

Company name:

Opusone

Company url, if any:

[BLANK]

If you have a demo, what’s the url? For non-software, demo can be a video.

(Please don’t password protect it; just use an obscure url.)

[BLANK]

Describe your company in 50 characters or less.

Read/Write DNA Device

What is your company going to make?

A cheap device to read and write DNA aimed at synthetic biology and DIYBio.

Which category best applies to your company?

Biotech

Is this application in response to a YC RFS?

No

Where do you live now, and where would the company be based after YC?

(List as City A, Country A / City B, Country B.)

Tokyo, Japan

CONTACT

Email address of the founder who is filling out this application:

XXXXXXXXXXXXXXX

Phone number(s):

XXXXXXXXXXX
FOUNDERS

Founders

HACKER NEWS USERNAME NAME EMAIL PROFILE UPDATED
new299 Nava Whiteford XXXXXXXXX yes
Please enter the url of a 1 minute unlisted (not private) YouTube or Youku video introducing the founders. (Follow the Video Guidelines.)

Please tell us about an interesting project, preferably outside of class or work, that two or more of you created together. Include urls if possible.

[BLANK]

How long have the founders known one another and how did you meet? Have any of the founders not met in person?

[BLANK]

PROGRESS

How far along are you?

Idea stage, in process of building proof of concept.

How long have each of you been working on this? Have you been part-time or full-time? Please explain.

1 month.

I started developing the concept about a month ago. I’ve ordered reagents, designed PCBs and sent them out for fabrication.

Which of the following best describes your progress?

Unlaunched

When will you have a prototype or beta?

within 6 months

Do you have revenue?

No

How much money do you spend per month?

1000

How much money does your company have in the bank now?

0

How long is your runway?

(e.g. 5 months)

6 months

If you’ve applied previously with the same idea, how much progress have you made since the last time you applied? Anything change?

[BLANK]

If you have already participated or committed to participate in an incubator, “accelerator” or “pre-accelerator” program, please tell us about it.

[BLANK]

IDEA

Why did you pick this idea to work on? Do you have domain expertise in this area? How do you know people need what you’re making?

I’ve worked at many different (5) DNA sequencing companies at various levels, up to CTO.

I feel like I have a good feel for the pain points in development and have developed a unique angle on sequencing.

I think this is an instrument that every synthetic biology or DIYBio lab needs.

What’s new about what you’re making? What substitutes do people resort to because it doesn’t exist yet (or they don’t know about it)?

Slow turn DNA synthesis or sequencing by an external lab.

Who are your competitors, and who might become competitors? Who do you fear most?

There are large sequencing companies (Illumina) and synthesis companies (Twist).

No-one is targeting something very cheap. Nobody is developing a single device to read and write DNA to my knowledge. An existing synthesis company could potentially pivot into this.

Someone suddenly decide to slash their sequencing costs by 1000 fold. A complete product could come out of the blue which does everything I’m considering, at the same cost, and with loads of money backing it.

What do you understand about your business that other companies in it just don’t get?

They want to grow the existing market. I want to build new ones.

How do or will you make money? How much could you make?

(We realize you can’t know precisely, but give your best estimate.)

I think the global market for DNA synthesis alone could grow to ~20BUSD.

How will you get users? If your idea is the type that faces a chicken-and-egg problem in the sense that it won’t be attractive to users till it has a lot of users (e.g. a marketplace, a dating site, an ad network), how will you overcome that?

I’d like to engage with the DIYBio community, and more traditional hacker spaces, and show what can be done with a read/write DNA instrument.

I would engage in early access projects with synthetic biology labs.

EQUITY

Have you incorporated, or formed any legal entity (like an LLC) yet?

No

If you have not formed the company yet, describe the planned equity ownership breakdown among the founders, employees and any other proposed stockholders.

(This question is as much for you as us.)

Solo founder. I have enough experience to build a proof of concept, but I will need to hire technical leadership. I will need guidance on this. I believe a decent CSO will require cofounder level equity for example (10%+).

Please provide any other relevant information about the structure or formation of the company.

[BLANK]

LEGAL

Are any of the founders covered by noncompetes or intellectual property agreements that overlap with your project? If so, please explain.

[BLANK]

Who writes code, or does other technical work on your product? Was any of it done by a non-founder? Please explain.

I’ve worked on everything so far.

Is there anything else we should know about your company?

(Pending lawsuits, cofounders who have left, etc.)

[BLANK]

OTHERS

If you had any other ideas you considered applying with, please list them. One may be something we’ve been waiting for. Often when we fund people it’s to do something they list here and not in the main application.

* Easy mail order water quality testing.
* Using nanopore for DNA synthesis.
* Offline collaboration tools for use in space.

Please tell us something surprising or amusing that one of you has discovered.

(The answer need not be related to your project.)

[BLANK]

CURIOUS

What convinced you to apply to Y Combinator?

I read hackernews, you seem to treat people fairly and I think would be good people to help me get things off the ground.

How did you hear about Y Combinator?

news.ycombinator.com

Gene Editing Companies (December 2018)

I’ve put together the list of Gene/Genome/DNA editing business below. I’ve listed companies who seem to be primarily service or research apps businesses below the main list, however the distinction isn’t always clear as they may have some novel technology as well as.

These are all the editing companies I’m aware of. If you know of any more, or have any corrections for the list, let me know!

Company Stage Raised Application Location Site/Info
Agenovir Acquired 10.6M antiviral therapies San Diego – USA report
ATGC Inc IPO nanoparticle delivery system Ann Arbor – USA grant info
Beam Therapeutics Series A 87M Base editor human therapeutics Cambridge – USA site
Biopalette Seed? ~2M Non-cutting Editing tech Kobe – Japan site
Caribou Biosciences Series B 74.6M Foundational CRISPR-Cas9 IP Bay Area – USA site
Celdara Medical CRISPR HIV Therapy New Hampshire – USA grant info
CELL MICROSYSTEMS INC. High throughput CRISPR cell-line production North Carolina – USA grant info
Cellectis IPO CAR-T (gene edited) for Cancer therapy France site
Cibus Series C 200M Gene editing crop development San Diego site
Crispa Therapeutics Series B 127M Foundational CRISPR IP – Human therapeutics Cambridge – USA site
Desktop Genetics Series A? 6.9M AI for CRISPR design London – UK site
Edigene Series A 15M Engineered CRISPR/Cas9 Tokyo – Japan site
Edit Force Series A ~4.5M PPR protein engineering tech. Fukuoka – Japan site
Editas Medicine IPO 210M CRISPR for human therapeutics Cambridge – USA site
eGenesis Bio Series A 40M Edited animals for xenotransplantation Cambridge – USA site
Eligo Bioscience (fka PhageX) Series A 22.9M Bacteriophage delivered CRISPR anti-microbials Paris – France site
Evotec AG IPO CRISPR licensee – research tools Hamburg – Germany report
Excision BioTherapeutics Seed 10M Human therapeutics Pennsylvania – USA site
Exonics Therapeutics Series A 45M SingleCut CRISPR for human therapeutics (neuromuscular) Watertown – MA – USA site
GenEdit pre-seed? CRISPR (+other) therapeutics with nanoparticle delivery Berkeley – USA site
Homology Medicines IPO 127M Homologous recombination for human therapeutics Bedford – MA – USA site
Inari Agriculture Series B 40M Editing for Agriculture applications Cambridge – USA site
indee labs Seed 5.1M Vortex shedding gene delivery for editing apps San Francisco – USA site
Inscripta Series C 84.4M Developing new classes of CRISPR endonuclease novel editing tech. Boulder – USA site
Ligandal Seed 844K Nanotech delivery platform for CRISPR human therapeutics San Francisco – USA site
Locus Biosciences Series A 26M CRISPR-engineered bacteriophage cocktails – human therapeutics North Carolina – USA site
Mammoth Biosciences Series A 24.6M CRISPR-based disease detection (human diagnostics) San Francisco – USA site
NextBiotics Seed 100K CRISPR edited bacterophage? San Francisco – USA site
Pairwise Plants Series A 25M Gene editing for agricultural applications North Carolina – USA site
Plantedit Seed 100K Gene editing for agricultural applications Indiana – USA. site
Poseida Therapeutics Series B 84.5M Novel Cas-CLOVER editing for human therapeutic applications San Diego – USA site
Precision BioSciences Series B 135.7M Homing endonuclease based editing platform North Carolina – USA site
Recombinetics Series A 60.9M xenotransplantation and edit humanized disease models Minnesota – USA site
Sangamo Therapeutics IPO 93.2M ZFN Gene editing for human therapeutics Richmond – USA site

Service Businesses

Company Stage Raised Application Location Site/Info
Allele Biotechnology Series B 10M Service business San Diego – USA site
Applied StemCells Series D 23.5M Service business San Francisco – USA site
GeneCopoeia CRISPR Service business Maryland – USA site
genoway Edited mice etc. Service business Lyon – France site
GenScript CRISPR Service Business New Jersey – USA site
Horizon Discovery IPO Editing Service Business Cambridge – UK site
HUDSON RIVER BIOTECHNOLOGY BV IPO Editing Service Business Netherlands site
inDroso CRISPR genome edited flies Service Business Rennes – France site
ThermoFisher Service Business site
MaxCyte IPO 31.3M Editing Services and tools Maryland – USA site
OriGene CRISPR Service business and products Maryland – USA site
Sigma Aldrich Service business and tools site
Synthego Series C 159.5M Service Business and tools for editing Redwood City – USA site
Taconic Biosciences Service business – CRISPR mouse models New York – USA site
ToolGen Service business -IP holder? Seoul – Korea site

Misc

BBI Life Sciences: www.bbi-lifesciences.com
Benchling – Design tool: site

QuantumSi

There’s very little public information about QuantumSi. Sequencing isn’t mentioned on the company website [1]. QuantumSi is part of the 4Catalyzer group of companies, founded by Johnathan Rothberg. Rothberg of course, previously founded sequencing companies 454 Life Sciences, and Ion Torrent. QuantumSi’s patents mostly list Rothberg as an inventor and are largely DNA sequencing related.

Technology

The QuantumSi approach as presented in patents appears to be similar to the Pacific Biosciences Zero Mode Waveguide platform:

QuantumSi and PacBio approaches from [2] and [3].

In this approach a polymerase is tethered to the bottom of a nanoscale well (ZMW). The well is illuminated, however because the well is smaller than the illumination wavelength the photons can not fully enter the well. Instead, you get an evanescent field confined within a few nanometers of the surface.

This is not unlike TIRF microscopy, which similarly confines illumination to within a few nanometers of a surface (and is used in Illumina sequencing [4]).

To sequence a strand of DNA the polymerase incorporates fluorescently labeled nucleotides. There are no terminators so nucleotides are incorporated in real time. During incorporation the fluoresces are cleaved and released. This results in a brief “flash” as the label is excited under the evanescent field.

These flashes need to be monitored in real time. This is were the QuantumSi and PacBio approaches appear to differ. Looking at RS and PacBio chips, it looks like PacBio moved from external camera in the RS to a fully integrated chip in the Sequel:

PacBio patents [5] suggest that they may use a fresnel lens integrated under the ZMW. Under the lens are multiple (appears to be 2) filters and sensor:

Integrating a fresnel lens onto a semiconductor device seems really neat. However I suspect this makes for a significantly non-standard (and more expensive) fabrication process.

The QuantumSi patents differ in terms of detection. Rather than using filters to detect labels with different excitation wavelength, the QuantumSi chips use intensity and decay rate to distinguish between different labels [6]:

I guess these may be standard fluorophores, but I’ve not dug into the patents to find out exactly what’s being used. While the patent mentions excitation “intensity” I’d assume that the photosensor responds with differing intensity to different wavelengths, so it could just be this that results in differing intensity between the fluorophores. The rate of fluorescent delay, provides a secondary signal to help distinguish between label types.

This approach most likely results in a cheaper chip, that can be more easily manufactured using a standard manufacturing process (as no lens or filters are required).

Given Illumina’s recent acquisition of Pacific Biosciences the potential for a low cost competitor to PacBio using a similar approach is interesting. I’ll be keeping an eye on QuantumSi, Rothberg has a track record of executing well, and I suspect we will hear more in the not too distant future.

Notes

[1] http://quantum-si.com/

[2] https://patents.google.com/patent/US20170362651A1

[3] https://patents.google.com/patent/US7973146B2

[4] https://blogs.swarthmore.edu/Illumina+GAIIx+Teardown/?p=27

[5] http://www.freepatentsonline.com/20180180548.pdf

[6] http://www.freepatentsonline.com/y2017/0349944.html

2018 DNA Sequencing Raises and Acquisitions

As we’re heading toward the end of 2018, I thought it might be interesting to put together a list of DNA sequencing companies that have raised in 2018. I’m aware of 14 companies that either raised or were acquired this year. Excluding acquisitions this totaled 368MUSD of investment.

Company Amount (MUSD) Further Info
Centrillion Biosciences 27.5 info
Direct Genomics 34 info
Genapsys 32.5 info
iNanoBio 3.3 info
LaserGen (acquired) 105 info
Omniome 60 info
Oxford Nanopore 140 info
Pacific Biosciences (acquired) 1200 info
Quantapore 15.55 info
Quantum Biosystems 8.8 info
QuantumDX 12 info
Stratos Genomics 20 info
Two Pore Guys 2.9+4.6? info
Universal Sequencing Technology 8 info

A couple of other companies raised toward the end of 2017:
Cygnus Biosciences, 19.6M USD info and
Base4 Innovation Ltd, 6.5M USD, info.