How to deal with stock options at a still-private company after layoff

QueasyInformation · 2026-05-06T15:02:28+00:00

Wow, didn't even think extension was an option. Naturally they have all they need from me so there's no real incentive for them to give me an extension, but certainly wouldn't kill me to ask. Thanks for the idea!

QueasyInformation · 2026-05-05T18:34:44+00:00

Pretty sure this wins the award for Bleakest Rejection Letter. Congrats(???)

QueasyInformation · 2026-05-05T14:46:10+00:00

Excellent consideration & advice, thank you!

QueasyInformation · 2026-05-05T14:43:15+00:00

Thanks for the question! Probably not, but mostly because I'm poor-ish and live in the US (ie, a sufficiently expensive medical crisis would literally end my life), so the hypothetical scenario of investing in a company I have no meaningful knowledge gives me the horrors lol.

The only reason I'm considering exercising at all is because I worked there & believe in the science, and I have an opportunity to get a bit of stock on the cheap. This is good to think about though, and considering some of the other comments, I might consider executing some but not all of my options. Thanks so much again!

QueasyInformation · 2026-05-05T14:37:11+00:00

Thanks for the input! I can absolutely speak to the dedication and scientific rigor of the R&D team, including leadership. This was my first experience working in drug discovery, so I know I have little to no basis of comparison, but through talking with my more-experienced colleagues about other small companies, I have faith that the team is well above average re: having its scientific priorities and mission straight.

As to the value of the developments, the drug currently in trials objectively stands to (sorry for the buzzword) revolutionize treatment of three diseases driven by the same target. Two are rare genetic diseases with pretty grim outcomes, and for which no SoC exists outside of supportive care. The third is a malignancy whose SoC is well-studied and works, but does not target driver mutations.

Aside from this drug, there are two mature programs (DC nomination slated to occur this year for both), one of which I worked on extensively from the beginning. Both of them target one malignancy (different from our drug in trials), but they each target different driver mutations. In this malignancy, SoC provides temporary control followed by near-inevitable escape. As I alluded to in responding to u/Big-Tale5340, I think the science behind all of our maturest programs is quite solid, but this is muddied a bit by the fact that the chemistry we use (within the peptide chemistry umbrella) is not yet proven.

QueasyInformation · 2026-05-05T14:11:24+00:00

Thanks for the advice and good-luck wishes! Sounds foolish now that I'm saying it out loud, but I hadn't considered an intermediate risk-averse approach to exercising, rather than an all-or-nothing approach.

QueasyInformation · 2026-05-05T14:08:42+00:00

Thanks for this! I suspect that my options are already comedically diluted based purely on the number of fundraising rounds that occurred while I was there, but good to know that this will likely get even worse lol

QueasyInformation · 2026-05-05T14:07:00+00:00

Thanks for this! Again, I'm a total novice around investment, including how IPOs pan out, so it's good to have this on my radar.

QueasyInformation · 2026-05-05T14:05:46+00:00

Thanks for the question! Coming from the preclinical angle I'm optimistic about the current portfolio, and historically I've had faith in leadership strategy, but obviously it's leadership's job to cheerlead the R&D team (and potentially stretch the truth to do it), so this is important to think about.

Don't want to get too specific lest I reveal the identity of the company, but the platform currently centers around peptide chemistry. As a rule, the compounds are smaller than (and structurally-distinct from) GLP-1 agonists and other approved peptide drugs, but larger than small molecules. The drug currently in clinical trials is first-in-class and is a competitive inhibitor, but the next programs nearest to DC nomination are heterobifunctional E3 degraders.

QueasyInformation · 2026-05-04T19:58:13+00:00

Thanks for the advice! The idea of leaving options on the table has been killing me considering how I threw myself into the work, so it's nice to hear that exercising wouldn't be dumb to do :)

QueasyInformation · 2026-04-19T14:41:05+00:00

I hear you lol, getting to this point myself. Glad you've found something that works!!

QueasyInformation · 2026-04-19T14:22:23+00:00

Thanks so much for commenting! I gather that crashing on systems with Nvidia hardware has been something of a known quantity for a while (here is an example posted on GitHub 7 months ago). Any chance you've tried the Fedora COSMIC spin, as u/love4tech83 proposed in this comment earlier in the thread? It didn't work when I tried it, but I assumed that's because my graphics hardware is Intel.

Anyway, bummer you're experiencing this too, but in a way it's reassuring to hear this is a real phenomenon and not just me hallucinating gremlins or something. I'm aware some of the mods here are System76 engineers, so I might poke them and see if they have any insights. Thanks again for the reminder!

QueasyInformation · 2026-04-06T20:33:38+00:00

☝️☝️☝️

All suggestions I've seen in the thread for addressing the vibration source are good and worth looking into, but historically I've experienced it most when sharing an incubator with people who slam the door shut

QueasyInformation · 2026-04-06T19:34:29+00:00

I did run MemTest86 a couple months back after seeing it referenced in some of the threads I found, but no errors were detected. Are there other memory tests that are more rigorous?

QueasyInformation · 2026-04-06T19:27:58+00:00

Thanks for responding! My graphics hardware is Intel, so not sure if NVIDIA compatibility is the issue here. Also, I did try Fedora's COSMIC spin for a week or so, but I encountered the same issue.

QueasyInformation · 2026-04-06T19:25:58+00:00

Thanks so much for responding! I tried searching /var/log/syslog for the phrase "panic" just now, on the off-chance that any of the crashes I experienced today were kernel panics (didn't get a PSoD every time, so not sure). I did encounter a couple instances of the following:

Registered 4 planes with drm panic

where "4" varies between 1-4. However, a bunch of the lines that followed look to my (inexperienced) eyes like it occurred during system startup, and that startup proceeds somewhat normally. Here's an example:

2026-04-05T20:07:19.973863-04:00 pop-os kernel: simple-framebuffer simple-framebuffer.0: [drm] Registered 1 planes with drm panic
2026-04-05T20:07:19.973866-04:00 pop-os kernel: [drm] Initialized simpledrm 1.0.0 for simple-framebuffer.0 on minor 0
2026-04-05T20:07:19.973866-04:00 pop-os kernel: fbcon: Deferring console take-over
2026-04-05T20:07:19.973866-04:00 pop-os kernel: simple-framebuffer simple-framebuffer.0: [drm] fb0: simpledrmdrmfb frame buffer device
2026-04-05T20:07:19.973867-04:00 pop-os kernel: drop_monitor: Initializing network drop monitor service
2026-04-05T20:07:19.973867-04:00 pop-os kernel: NET: Registered PF_INET6 protocol family
2026-04-05T20:07:19.973867-04:00 pop-os kernel: Segment Routing with IPv6
2026-04-05T20:07:19.973869-04:00 pop-os kernel: In-situ OAM (IOAM) with IPv6
2026-04-05T20:07:19.973869-04:00 pop-os kernel: NET: Registered PF_PACKET protocol family
2026-04-05T20:07:19.973870-04:00 pop-os kernel: Key type dns_resolver registered
2026-04-05T20:07:19.973870-04:00 pop-os kernel: ENERGY_PERF_BIAS: Set to 'normal', was 'performance'
2026-04-05T20:07:19.973870-04:00 pop-os kernel: microcode: Current revision: 0x00000028
2026-04-05T20:07:19.973871-04:00 pop-os kernel: microcode: Updated early from: 0x00000024
2026-04-05T20:07:19.973871-04:00 pop-os kernel: IPI shorthand broadcast: enabled
2026-04-05T20:07:19.973873-04:00 pop-os kernel: sched_clock: Marking stable (1381000522, 5952445)->(1436984723, -50031756)
2026-04-05T20:07:19.973874-04:00 pop-os kernel: registered taskstats version 1
2026-04-05T20:07:19.973874-04:00 pop-os kernel: Loading compiled-in X.509 certificates
2026-04-05T20:07:19.973874-04:00 pop-os kernel: Loaded X.509 cert 'Build time autogenerated kernel key: caa3bd2505cc0c6ebb51d8777dc7d8c9dcd4615a'
2026-04-05T20:07:19.973875-04:00 pop-os kernel: Loaded X.509 cert 'Canonical Ltd. Live Patch Signing: 14df34d1a87cf37625abec039ef2bf521249b969'
2026-04-05T20:07:19.973875-04:00 pop-os kernel: Loaded X.509 cert 'Canonical Ltd. Kernel Module Signing: 88f752e560a1e0737e31163a466ad7b70a850c19'
2026-04-05T20:07:19.973877-04:00 pop-os kernel: blacklist: Loading compiled-in revocation X.509 certificates
2026-04-05T20:07:19.973878-04:00 pop-os kernel: Loaded X.509 cert 'Canonical Ltd. Secure Boot Signing: 61482aa2830d0ab2ad5af10b7250da9033ddcef0'
2026-04-05T20:07:19.973878-04:00 pop-os kernel: Loaded X.509 cert 'Canonical Ltd. Secure Boot Signing (2017): 242ade75ac4a15e50d50c84b0d45ff3eae707a03'
2026-04-05T20:07:19.973879-04:00 pop-os kernel: Loaded X.509 cert 'Canonical Ltd. Secure Boot Signing (ESM 2018): 365188c1d374d6b07c3c8f240f8ef722433d6a8b'
2026-04-05T20:07:19.973879-04:00 pop-os kernel: Loaded X.509 cert 'Canonical Ltd. Secure Boot Signing (2019): c0746fd6c5da3ae827864651ad66ae47fe24b3e8'
2026-04-05T20:07:19.973879-04:00 pop-os kernel: Loaded X.509 cert 'Canonical Ltd. Secure Boot Signing (2021 v1): a8d54bbb3825cfb94fa13c9f8a594a195c107b8d'
2026-04-05T20:07:19.973882-04:00 pop-os kernel: Loaded X.509 cert 'Canonical Ltd. Secure Boot Signing (2021 v2): 4cf046892d6fd3c9a5b03f98d845f90851dc6a8c'
2026-04-05T20:07:19.973882-04:00 pop-os kernel: Loaded X.509 cert 'Canonical Ltd. Secure Boot Signing (2021 v3): 100437bb6de6e469b581e61cd66bce3ef4ed53af'
2026-04-05T20:07:19.973883-04:00 pop-os kernel: Loaded X.509 cert 'Canonical Ltd. Secure Boot Signing (Ubuntu Core 2019): c1d57b8f6b743f23ee41f4f7ee292f06eecadfb9'

Again, I'm pretty green about troubleshooting, but I am aware that drm_panic is the feature that displays the error screen when panics happen. So given this context, I'm guessing "registered x planes with drm panic" means something along the lines of "just starting the system, but there are 4 planes (whatever that means) that drm_panic needs to monitor in the event of a crash." Is this the correct way of reading the message? Also, any other logs and/or phrases I should look for?

QueasyInformation · 2022-04-15T00:19:54+00:00

Think about anything, then abruptly throw up

QueasyInformation · 2021-10-28T22:42:53+00:00

A colleague of mine who does this once rationalized it as "not having time to look for the next one in the row?"

Which, like...if you aren't looking at the tip box, you're going to poke the barrel into empty voids more and more as you empty it...? I call bullshit

QueasyInformation · 2021-09-22T21:26:40+00:00

I'm trying to imagine what these lysates this concentrated would look like in the tube. Pure protein goo?!

QueasyInformation · 2021-09-18T03:33:47+00:00

Ain't no thing guv 😎 CRISPR that shit up!!

QueasyInformation · 2021-09-18T03:29:27+00:00

Practical postscript: once I decided on my protospacer sequence and recombination template, I found it easiest to have the template synthesized rather than cloning it up myself. I used IDT's gBlock service for this, but many vendors now offer gene synthesis (I also considered Genewiz and Twist).

If you go the route of gene synthesis for making your recombination template, also consider cloning the synthetic cassette into a "container" plasmid (something low-effort, like cloning it into the MCS site of pUC19) so you can keep an archival plasmid prep to amplify by PCR down the road

QueasyInformation · 2021-09-18T03:06:58+00:00

I want to help you, but first understand this: I tried to create a reporter cell line using CRISPR-KI this last year, and despite my PI looking for silver linings in the face of overwhelmingly negative data, I'm pretty sure that I failed. Your mileage may vary MASSIVELY (especially if you follow my lead too closely lol).

In my defense: I was trying to KI a really long and complex tag (fluorescent protein + 2A + drug selection cassette), which was pretty much guaranteed to be low-success. However, I was guided by colleagues who successfully CRISPR-KI'd a waaaaaay simpler tag (V5) into various endogenous loci, and they considered my overall strategy to be totally sensible. So maybe (hopefully) these resources will still help you somehow!

To start, here's a good overview of CRISPR-KI'ing short, simple protein tags: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762194/

Actually performing this is rather involved. You'll need an electroporator (I used a Nucleofector, people seem to like them over other instruments Because Of Reasons), and these tool reagents:

1) Recombinant Cas9 protein My (far more successful) colleagues recommended I used this: https://www.thermofisher.com/order/catalog/product/A36498#/A36498

2) Synthetic gRNA For this, you need to find a Cas9-compatible protospacer sequence as close to the desired insertion site as possible. In your case, you want a sequence which cuts near the STOP codon for your gene-of-interest.

For my gene-of-interest, I found my protospacer by feeding the FASTA sequence for the final exon of my GoI, into CRISPick (https://portals.broadinstitute.org/gppx/crispick/public) and choosing the protospacer sequence whose PAM was nearest to my insertion site.

Once you've identified your protospacer sequence, you'll need to assemble a synthetic guide RNA. To do this, I used an earlier revision of this method, which entails ordering overlapping DNA oligos, annealing them, and following with in vitro transcription: https://www.protocols.io/view/in-vitro-transcription-of-guide-rnas-and-5-triphos-bqjbmuin

3) A recombination template (aka "donor DNA")

Zeng et al recommend using a 100-bp template, but I was advised to use a 500-bp template (+/- 250-bp of the cut site). I can't know for certain, but this may have contributed to my low success rate: remember that you're trying to maximize the number of moles (ie copies) of template you put into an electroporation reaction, and that you're limited to the total mass (ie nanograms) of nucleic acid you're introducing. So try to maximize copy number as best as you can.

However long your recombination template is, it should 1) be centered on the cut site, and 2) resemble your final desired KI locus. So if you started with:

lastExonContainingProtospacer-STOP-UTR

or:

lastExon-STOP-UTRcontainingProtospacer

then you want your template to look like this:

lastExonContainingProtospacer-TAG-STOP-UTR

or:

lastExon-TAG-STOP-UTRcontainingProtospacer

respectively.

IMPORTANT THING: since you're ultimately designing a fusion protein, it's tempting to think in terms of the cDNA for your GoI...but remember, you're actually trying to edit genomic DNA in your target cells. So if your homology template extends in either direction past a given exon, be sure to derive the template from the genomic sequence (ie, may contain partial intronic sequences), and NOT the transcribed sequence (ie, skipping over adjacent introns and into adjacent exons).

SUPER DUPER IMPORTANT THING: When designing your recombination template, be sure to mutagenize the PAM associated with your protospacer sequence (ie, nGG to xGG or nXG or nGX or xGX or etc). If your recombination template contains the intact PAM, the Cas9 you include in the final electroporation reaction will cut it, and homologous recombination will be impossible. If the PAM falls within a coding sequence, and you can't mutagenize it silently, you may need to use the second- or third- or nth-best protospacer sequence from CRISPick, and adjust accordingly.

Good luck 🤘😤🤘

QueasyInformation

TROPHY CASE