Over the past year, I watched a founder of an innovative cancer therapeutics company spend eight months chasing a meeting with one of biotech's most prestigious VCs.

She had everything working in her favor: a compelling platform, strong preclinical data, a former pharma exec in her c-suite. She got the warm intro. She sent the deck. She followed up. And followed up again.

Finally, after months of back-and-forth and a nudge from an Associate through another warm intro, she got the meeting. The partner was engaged, asked great questions, and said he'd bring it to the team.

Then silence.

Four weeks later, she got the email: "We love the mechanism and the team. But we'd need to see GLP tox completed and a clearer line of sight to IND before we could lead."

She read it twice.

GLP tox was exactly what this raise was supposed to support. The VC fund wanted the data that would only exist after someone wrote the check.

This is the biotech “valley of death” in one email: the investors who have the firepower to write big checks often won't move until the risk is gone. But removing the risk requires the capital that you’re raising in the first place.

Here's what she didn't know going in: That fund focus had shifted.

Their website still said "seed to Series A." But post-2021, their appetite changed. What used to be "early stage" now meant IND-ready. The partners were still taking meetings with preclinical companies - but the investment committee wasn't approving them the same as they did when the fund established its reputation.

Eight months. Dozens of follow-up emails. Countless hours of preparation. For a "no" that was almost predetermined before she ever walked in the room.

This is the brand name trap.

The funds everyone knows - the ones that keynote JPM and show up in TechCrunch headlines - have earned their reputations. They've built billion-dollar companies. Their names on your cap table mean something.

But reputation and fit are different things.

A fund that's perfect for your Series B might be structurally unable to lead your seed. A partner who built their career on clinical-stage assets may not have the mandate to go earlier. The biggest names in biotech VC might not be your best first call.

Today, I'm going to show you how established VCs actually work - their structures, their hierarchies, how decisions get made - so you can target strategically instead of chasing logos.

To be clear: I'm not saying big funds are “bad” or that they're out to get you - quite the contrary. These funds have built iconic companies, and their partnership can be transformative.

But if you've been following this series, you already know: fundraising is a full-time job (and then some). And as a founder, you only have 24 hours in a day - with experiments to run, employees to manage, and oh yeah, probably a family that would still like to see you for dinner :)

So this isn't about avoiding established VCs. It's about spending your time wisely and lining up your ducks so you can create the biggest leverage for your efforts.

Let's break down how to do exactly that.

Last week, we explored why micro-VCs and emerging managers might be your best first institutional partners. But established VCs, the funds with hundreds of millions or billions under management, aren't irrelevant to your fundraise. They're just a different tool for a different job.

Understanding how they work lets you use them strategically rather than chasing names and headlines.

Not all established VCs are the same. The differences in structure directly affect whether they can invest in you.

Mid-Size Funds ($100M-$500M)

These funds sit in a sweet spot. They're large enough to have institutional resources (dedicated partners, portfolio support teams, follow-on reserves) but small enough that a $500M exit still moves the needle.

Typical profile:

Many mid-size funds explicitly position themselves as "first institutional money in." They'll lead seed rounds and support companies through multiple rounds. For pre-seed founders, these are often your most realistic established VC targets.

Mega-Funds ($1B+)

The household names. Flagship, ARCH, Third Rock, a16z Bio. These funds have built legendary companies and their track records speak for themselves.

But the math works differently:

As we covered last week, a $500M exit returns 1.5x of a $50M micro-VC fund but barely moves a $2B mega-fund. This isn't a criticism, it's just math. Mega-funds need massive outcomes, which means they often prefer later-stage companies or companies with star-power founding teams, where the risk/reward profile fits their model.

Dedicated life sciences vs. generalist with healthcare allocation

This distinction matters more than most founders realize.

Dedicated life sciences funds (OrbiMed, RA Capital, Omega Funds) invest exclusively in healthcare and biotech. Their partners have deep domain expertise - often PhDs, MDs, or former pharma executives. They understand your science, your regulatory path, and your competitive landscape.

Generalist funds with healthcare allocation (Andreessen Horowitz, General Catalyst, GV) invest across sectors but have dedicated healthcare or bio partners. As a founder, you will benefit from broader networks, especially in tech-enabled biotech. However, you may be competing for allocation with AI companies, fintech, and consumer startups.

Neither is inherently better. But knowing which type you're approaching helps you tailor your pitch and set realistic expectations.

One of the biggest mistakes founders make is targeting the wrong person at the right fund.

The typical VC hierarchy:

Managing Partners / General Partners (GPs)

Partners

Principals / Vice Presidents

Associates / Analysts

A common misconception:

Many founders assume they need to reach the senior partner to get a deal done. Sometimes the opposite is true.

A principal who's building their track record needs to find great companies. They're hungry. They'll take more meetings, respond faster, and work harder to champion your deal internally. If they bring you to the partnership and the deal works, it advances their career.

A managing partner with 20 years of wins already? They can afford to be selective. Your deal is one of hundreds they'll see this quarter.

This doesn't mean senior partners are bad targets, especially if you have a genuine relationship or warm intro. But if you're doing cold outreach, targeting hungry mid-level investors often yields better results.

How decisions actually get made:

Most established VCs use an investment committee (IC) process:

The timeline from first meeting to term sheet is typically 6-12 weeks for established VCs, sometimes longer. This is structurally slower than micro-VCs and emerging managers, which is why being strategic where these relationships fit within your fundraise is important.

Here's the reality: You only have 24 hours in a day. On top of running your company, managing your team, advancing your science, and everything else on your plate - you need to be strategic about where you spend fundraising energy.

When established VCs make sense:

You're raising Series A or later. This is the sweet spot for most established funds. You have data, you've de-risked key questions, and you need the larger checks they write.

You're raising a large seed ($5M+). Some mid-size funds and even select mega-funds will lead substantial seed rounds, especially for experienced teams or differentiated platforms.

The fund explicitly invests at your stage. Look for language like "first institutional check," "company creation," (if that’s something that you’re comfortable with) or "seed and Series A focus." Check their portfolio for recent pre-seed or seed investments.

You have a genuine relationship. If you have a friendly connection at a big fund (e.g. someone you've known for years, a former colleague, a mutual collaborator) by all means take that meeting. Keep them posted on your progress well before your raise. These relationships, when authentic, can become powerful when the timing is right.

When to deprioritize:

You're pre-seed with no warm path in. Cold outreach to mega-funds at pre-seed has very low conversion. Generally, I am actually a believer in cold outreach when done right, but at big funds, the supply/demand is most often not in your favor.

The fund hasn't invested at your stage in 2+ years. Past behavior predicts future behavior. If their last seed investment was 2021, they've likely moved upstream.

You're burning cycles on "stay warm" meetings. Some investors will take meetings as part of general market research/staying up to date on a market (unfortunate, but true). If you've had multiple "update" calls with no forward progress, reallocate that time or ask for more direct feedback.

A more strategic approach

Think of established VCs in three buckets:

Relationship-first (warm connections): Take the meeting. Keep them updated quarterly. When timing aligns, they'll already know your story.

Research-first (no connection yet): Build the relationship before you need it. Engage with their content. Get introduced through portfolio founders. Aim to be on their radar before you're actively raising.

Later-round targets: Add them to your tracker, but don't spend pre-seed cycles chasing them. They'll still be there when you're ready for Series A.

A note on corporate VC:

For this issue, I’m purposely leaving corporate venture arms (Pfizer Ventures, Lilly Ventures, J&J Innovation, etc.) out of this week's coverage. They operate differently, with strategic mandates layered on top of financial returns, and deserve their own deep dive (let me know if you’d like to see this!).

As a quick refresher: Source builds your initial list, Isolate identifies who's actively deploying at your stage, Filter qualifies who can truly help, and Tier prioritizes by fit and access path.

SOURCE: Building your established VC universe

Start with the obvious sources:

Go deeper:

Build a list of 30-50 established funds that could invest in companies like yours.

ISOLATE: Signals they're active at your stage

Not every established fund is right for you right now. Look for:

Recent fund close (past 18 months): Fresh capital means active deployment. Funds in years 1-3 of their cycle are most aggressive.

Stage-appropriate investments in the past 12 months: Check website announcements, Crunchbase or PitchBook for recent deals at your stage.

Thesis alignment: Does their stated focus match your company? Platform vs. asset, modality focus, therapeutic area.

Check size fit: If they typically write $20M checks (at de-risked stages) and you're raising a $3M seed, the math won’t be in your favor.

Yellow flags: Fund closed 3+ years ago (may be mostly deployed). No investments at your stage in 18+ months. Recent partner departures in your focus area.

FILTER: Can they be a true partner?

Beyond the check, what do they bring?

Ask:

The best way to answer these: Talk to portfolio founders. Not the ones in the select press releases, but all the “other” ones - find them through LinkedIn and ask for candid feedback.

TIER: Prioritize by fit and access

Tier 1 (active pursuit):

Tier 2 (build relationship):

Tier 3 (later round):

This week, you're building your established VC pipeline - strategically. The goal: 20-30 qualified funds in your tracker, properly tiered by fit and timing, with a clear understanding of who actually makes decisions at each one.

Start by mapping the established VC landscape for your specific sector and stage.

Target: 25-35 funds

Now go deeper into how each target fund actually operates. The goal: know exactly who to reach and how decisions get made before you ever send an email.

Target: Top 15 funds with decision-makers mapped

Time to prioritize. Not every established VC belongs in your active pipeline - the key is knowing which ones to pursue now, which to nurture, and which to save for later rounds.

Target: Final tiered list with clear next steps for each

Next week, we'll have our Fundraising Intensive Graduation (yay!) with tools, templates, and the complete system for managing your investor pipeline - so all the work you've done over the past 6 weeks comes together into one actionable workflow.

I've put together a comprehensive resource to help you target established VCs strategically and methodically and not get caught up in the logos and FOMO.

What's Inside:

Established VC Directory - 100+ life sciences VCs with details by sector, fund size, check size range, notable deals, and direct links. Your starting point for strategic targeting.

[Download the Established VC Sourcing Kit]

And an extra holiday bonus: AI Research Mega-Prompt - Paste this into your favorite AI tool to identify which established VCs are the best fit for your specific company. Input your sector, stage, therapeutic area, and raise size and get back a prioritized target list with rationale & guidance.

[Grab your Established VC Mega-Prompt Here]

You now have a complete playbook for sourcing and qualifying micro-VCs and emerging fund managers.

This week, here’s your mission, should you choose to accept it 🙂: build your established VC pipeline strategically. Research 25-35 funds, map the hierarchy at your top 15, and tier them by fit and timing. Remember: reputation and fit are different things. The biggest names might not be your best first call.

Next Sunday, we're holding our Fundraising Intensive Graduation! To celebrate, I’ll be sharing tools, templates, and the complete system for managing your investor pipeline. Don’t miss it!

I'd love to hear from you: How has your experience been with “brand name” VCs? Is there anything I missed, or have you had a different experience? Reply and let me know, I’d love to hear your story!

See you next Sunday!

To your success,

- Vadim

PS: How are you spending the holidays? Are you traveling, doing anything fun, or holding down the fort? Let me know, I’d love to hear from you!

PPS: If you have someone on your team helping with fundraising or know another founder who could benefit from this intensive, forward them this email. They can sign up to join us here: [Join the Intensive]