Founder Mode: Jen Herbach, Founder & CEO, Adventris Pharmaceuticals

Cancer Vaccine Technology

Adventris Pharmaceuticals is developing revolutionary cancer vaccines that work by educating the immune system to recognize and attack cancer cells it previously couldn't detect.

The Core Problem:

• Immune System Failure: Cancer fundamentally represents a failure of your immune system to recognize uncontrolled cells as foreign
• Hidden Threat: People get microscopic cancers all the time, but normally the immune system recognizes and eliminates them
• Recognition Gap: Deadly cancers occur when the immune system fails to identify these abnormal cells

The Solution - "Glasses for the Immune System":

1. Educational Approach: Cancer vaccines train the immune system to see what it previously couldn't detect
2. Visual Analogy: Like giving the immune system glasses to recognize threats it was blind to before
3. Targeted Recognition: Enable immune response against specific cancer-driving mutations

Key Advantages:

• Minimal Side Effects: Comparable to standard vaccines like flu shots or COVID vaccines
• Broad Application: Potential to prevent multiple cancer types through single targets
• Prevention Focus: Long-term vision includes preventing cancers before they develop

Timestamp: [0:27-1:26]

KRAS: The Master Cancer Driver

KRAS represents one of the most significant targets in cancer treatment, affecting over 30% of all cancers and driving some of the deadliest forms of the disease.

KRAS Mutation Mechanics:

• Driver Mutation: KRAS transforms healthy cells into cancerous ones through a specific genetic change
• Uncontrolled Growth: Once mutated, KRAS leads to uncontrolled cell division and tumor formation
• Critical Transformation: The mutation marks the exact moment a healthy cell becomes cancerous

Cancer Types Affected:

1. Lung Cancer - Major KRAS-driven malignancy
2. Colon Cancer - Significant KRAS mutation presence
3. Pancreatic Cancer - Primary initial target for Adventris

Strategic Impact:

• 30% Coverage: KRAS mutations cause over 30% of all cancers
• Deadly Targets: Focuses on some of the most lethal cancer types
• Prevention Potential: Future vision includes preventing 30% of all cancers through KRAS targeting
• Broad Application: Single vaccine approach for multiple cancer types

Treatment Approach:

• Immune Education: Train immune system to recognize KRAS-mutated cells
• Early Intervention: Target localized disease before metastasis occurs
• Curative Intent: Potential to cure patients of their disease at critical intervention points

Timestamp: [1:41-3:06]

Strategic Focus on Pancreatic Cancer

Adventris chose pancreatic cancer as their initial target due to its devastating prognosis and the critical intervention opportunity it presents.

Pancreatic Cancer Challenge:

• Incredibly Deadly: Among the most lethal cancer types with poor survival rates
• Inevitable Progression: Most patients with localized disease eventually develop metastatic, incurable disease
• Limited Treatment Options: Current therapies provide minimal long-term survival benefits

Strategic Treatment Timing:

1. Localized Disease Focus: Target patients before cancer spreads beyond the pancreas
2. Prevention of Metastasis: Intervene at the critical window before disease becomes incurable
3. Curative Potential: Opportunity to actually cure patients at this intervention point

Broader Vision:

• Treatment to Prevention: Long-term goal of moving from treatment into cancer prevention
• Blue Sky Vision: Ultimate aim to prevent 30% of all cancers through KRAS targeting
• Most Deadly Cancers: Focus on preventing the cancers with the worst outcomes

Patient Impact:

• Life-Saving Intervention: Transform inevitable death sentence into potential cure
• Quality of Life: Minimal side effects compared to traditional cancer treatments
• Hope for Families: Provide real hope for patients facing terminal diagnoses

Timestamp: [2:25-3:06]

Minimal Side Effect Profile

Adventris cancer vaccines demonstrate remarkably mild side effects, comparable to standard infectious disease vaccines that people routinely receive.

Side Effect Comparison:

• COVID Vaccine Level: Similar side effect profile to COVID-19 vaccines
• Flu Shot Equivalent: Comparable to annual influenza vaccinations
• Less Than Shingles: Actually milder than shingles vaccines, which tend to have more pronounced side effects

Real-World Context:

• Manageable Discomfort: Temporary illness lasting 1-2 days, similar to standard vaccine responses
• Acceptable Trade-off: Minor temporary discomfort in exchange for cancer prevention potential
• Routine Tolerance: Side effects within the range people already accept for preventive healthcare

Patient Perspective:

• Worthwhile Exchange: Patients willing to experience temporary vaccine side effects to prevent cancer
• Familiar Experience: Side effect profile matches what people already know and accept from other vaccines
• Quality of Life: Minimal impact on daily activities compared to cancer treatment alternatives

Safety Profile:

• Well-Tolerated: Vaccine approach avoids the severe side effects associated with chemotherapy and radiation
• Predictable Response: Side effects follow established patterns from other vaccine technologies
• Short Duration: Temporary discomfort rather than ongoing treatment-related complications

Timestamp: [3:12-3:42]

Clinical Development Timeline

Adventris is approaching critical regulatory milestones with plans to begin human trials in early 2027.

Current Development Stage:

• Product Finalization: Nearly completed defining the exact vaccine product for human trials
• IND Preparation: Preparing Investigational New Drug (IND) application for FDA submission
• Regulatory Package: Assembling comprehensive data package required for human testing approval

FDA Approval Process:

1. IND Application: Submit investigational new drug application to FDA
2. FDA Review: Regulatory review of safety and manufacturing data
3. Approval to Proceed: FDA clearance to begin human clinical trials
4. First Patient Dosing: Target early 2027 for initial patient treatment

Timeline Considerations:

• IND Turnaround: FDA typically processes IND applications relatively quickly
• Preparation Intensive: Most time investment goes into preparing the comprehensive application package
• Manufacturing Readiness: Ensuring product quality and consistency for human use

Regulatory Strategy:

• Standard Pathway: Following established regulatory framework for cancer vaccines
• Safety Focus: Comprehensive safety data package to support human testing
• Clinical Design: Structured approach to demonstrate vaccine efficacy and safety

Timestamp: [3:50-4:35]

Dream Team Co-Founders

Adventris was founded by college roommates who took different paths but shared the same vision of revolutionizing cancer treatment.

Jen Herbach's Journey:

• Science Foundation: Undergraduate degree in sciences with initial medical school aspirations
• Career Pivot: Originally planned to become an oncologist but stepped away due to emotional concerns about daily exposure to death
• Persistent Passion: Maintained lifelong commitment to working on cancer therapeutics
• Business Development: Pursued graduate school and business school to build startup capabilities
• Industry Experience: Spent entire career in life sciences bringing novel oncology drugs to market

Co-Founder Partnership:

• College Roommates: Founded company with college roommate and lab partner
• Complementary Paths: Co-founder pursued medical school and became an oncologist
• Shared Classes: Worked together as lab mates and academic partners throughout college
• Long-term Vision: Always planned to co-found a company together
• Perfect Combination: Business expertise paired with medical/clinical knowledge

Founding Motivation:

• Personal Mission: Lifelong desire to bring cancer therapeutics to market
• Entrepreneurial Drive: Always wanted to co-found own company rather than work for others
• Complementary Skills: Combining business acumen with medical expertise
• Shared Purpose: United vision of transforming cancer treatment and prevention

Timestamp: [4:39-5:39]

Transformative Startup Education

Y Combinator provided crucial startup knowledge that complemented Adventris's deep life sciences expertise, fundamentally changing their approach to building and presenting their company.

Knowledge Gap Identification:

• Life Sciences Strength: Team had deep expertise in life sciences and drug development
• Startup Weakness: Lacked fundamental knowledge about founding and building companies
• Story Telling Challenge: Struggled with effectively communicating their vision and value proposition

Key Y Combinator Benefits:

1. Story Development: Learned how to effectively tell their company story and articulate their mission
2. Investor Relations: Gained crucial skills for talking to and engaging with investors
3. Power Dynamics: Shifted from reactive to proactive position in investor conversations
4. Driver's Seat: Felt empowered and in control during investor interactions

Transformation Impact:

• Communication Skills: Dramatically improved ability to present complex science in compelling ways
• Investor Confidence: Changed dynamic from being evaluated to leading conversations
• Strategic Positioning: Better understanding of how to position company in market
• Founder Empowerment: Increased confidence in leading investor discussions

Recommendation Pattern:

• Strong Advocacy: Actively recommends Y Combinator to other life sciences companies
• Proven Value: Demonstrates clear ROI for science-heavy startups
• Skill Complementarity: Perfect match for teams with deep technical knowledge but limited startup experience

Timestamp: [5:51-6:32]

Founder Mode Revelation

Brian Chesky's founder mode talk provided a pivotal moment that transformed Jen's management philosophy and directly addressed critical challenges at Adventris.

Pre-Talk Management Mistake:

• Hands-Off Science: Believed she shouldn't manage day-to-day science operations due to her business background
• Delegation Philosophy: Operated under "scientists should manage science" principle
• Background Concern: Felt her business-focused background disqualified her from science management

Company Performance Issues:

1. Slow Progress: Company wasn't making expected advancement in research and development
2. Personnel Problems: Experiencing significant staff and management issues
3. Leadership Struggle: Uncertain about appropriate intervention strategies

Founder Mode Impact:

• Universal Recognition: Realized even successful companies like Airbnb face similar management challenges
• Scale Independence: Problems exist regardless of company size - small companies experience same issues as large ones
• Permission to Lead: Talk gave her permission to directly manage areas of expertise

Management Philosophy Shift:

• Direct Science Management: Embraced hands-on approach to scientific operations
• Detail Orientation: Committed to being "in the weeds" and involved in all details
• Founder Authority: Recognized founder's responsibility to manage all critical aspects regardless of background

Immediate Action:

• Timely Application: Talk came at perfect moment when struggling with these exact issues
• Confidence Building: Provided validation for more direct management approach

Timestamp: [6:55-7:58]

Essential Insights:

1. Revolutionary Cancer Approach - Adventris develops cancer vaccines that educate the immune system to recognize previously undetectable cancer cells, like giving the immune system "glasses"
2. KRAS Target Strategy - Focusing on KRAS mutations that drive over 30% of all cancers, starting with pancreatic cancer treatment with vision for prevention
3. Founder Mode Application - Brian Chesky's founder mode talk directly solved Jen's management struggles, empowering her to directly manage science operations despite business background

Actionable Insights:

• Cancer vaccines offer minimal side effects comparable to standard vaccines while providing potential cures
• Y Combinator transforms life sciences companies by teaching startup fundamentals and investor relations
• Founders should manage critical operations regardless of background when company performance suffers
• Strategic regulatory planning enables life sciences startups to reach human trials efficiently
• College partnerships can create powerful co-founder combinations with complementary expertise

Timestamp: [0:00-7:58]

Immediate Implementation of Founder Mode Principles

After attending Brian Chesky's founder mode talk, Jen immediately implemented daily accountability measures with her team:

Initial Implementation:

• Daily End-of-Day Standups: Required all team members to meet at the end of each day to report what they accomplished
• Direct Oversight: "I want to make sure you did it" - focused on verification and accountability
• Immediate Pushback: Team complained within the first weekend about the new requirements

Team Response and Natural Selection:

• Two People Quit: Team members who weren't aligned with the new accountability structure left the company
• One Team Member Thrived: The remaining employee who was comfortable with daily reporting flourished and became a strong contributor
• Strategic Hiring: Brought on new team members who were "really strong and on top of it"

Evolution of the Process:

1. Started: Daily end-of-day meetings for every team member
2. Questioned: New strong team members asked "Do we need these stand-ups?"
3. Maintained Principle: Kept the accountability structure to ensure continued team performance
4. Adjusted Frequency: Reduced from daily to three times per week due to improved team productivity

Timestamp: [8:00-9:12]

Redefining Leadership Terminology and Approach

The hosts and Jen discussed the need to rebrand "micromanaging" as it has proven highly effective for founders:

The Terminology Problem:

• Current Negative Connotation: "Micromanaging" suggests controlling every detail and telling people exactly what to do
• Actual Founder Mode Practice: Understanding what team members are doing through daily check-ins and accountability
• Proposed Alternatives: "Partnering" or "Accountability Partner" to better reflect the collaborative nature

The Evolution Process:

1. Initial Phase: Get deeply into the weeds and know everything happening
2. Team Development: Bring people up to speed with your leadership style and expectations
3. Gradual Pullback: Reduce oversight frequency as team demonstrates competence and alignment
4. Maintained Accountability: Continue structured check-ins but adjust based on team performance

Co-founder Dynamics:

• Single Attendee: Only Jen attended the retreat, not her co-founder
• Supportive Response: Co-founder's attitude was "As long as you're the one doing it, I'm fine with it"
• Clear Leadership: Established Jen as the primary implementer of the new management approach

Timestamp: [9:13-10:24]

Strategic Board Independence and Scientific Decision-Making

Jen's experience demonstrates the power of maintaining board control when facing investor pressure:

The YC Advice Foundation:

• Partner Guidance: Serby (now at Colate) advised to reject board seat requests from investors
• Trust-Based Approach: "If she tells me what to do, it's probably right and I'm going to listen to it"
• SAFE Structure: All funding done on SAFEs with no board members initially

The Scientific Disagreement:

• Investor Challenge: Investor questioned their scientific strategy and approach
• Founder Expertise: "We know the science so much better than they do" - investors had experience in different fields
• Firm Rejection: After considering feedback, definitively said "no, this is not the right approach"

Consequences and Benefits:

• Immediate Fallout: Investor didn't participate in the next funding round
• Investor Respect: Other investors recognized and respected their decision to stand firm
• Decision Speed: Able to make strategic pivots quickly without board approval processes
• Dual Focus: Decisions driven by "what's best for patients and what is the science and data telling us"

Timestamp: [10:36-13:56]

Prioritizing Board Control Over Valuation

Jen has developed a strategic approach to future fundraising that preserves founder autonomy:

Current Board Structure:

• Second Seed Round: Completed on SAFE structure, no priced round
• No Investor Board Members: Still just the founders on the board
• Independent Addition: Recently added an experienced biotech consultant as an independent board member by choice

Future Funding Strategy:

• CEO Consultation: Actively talking to other YC and life sciences CEOs about retaining board control
• Priority Hierarchy: Board control ranked as higher priority than valuation
• Valuation Trade-off: Willing to accept "slightly lower valuation to retain control"
• Proven Benefits: Having experienced the advantages of independence, strongly aligned with this approach

Industry Reality:

• High Capital Requirements: Human trials are "absurdly expensive" requiring significant future funding
• Strategic Planning: Already thinking about how to structure Series A while maintaining independence
• Experienced Guidance: Learning from other founders who successfully navigated similar challenges

Timestamp: [14:04-15:46]

Essential Insights:

1. Immediate Implementation Works - Jen successfully implemented daily standups right after the founder mode talk, leading to natural team selection where aligned employees stayed and unaligned ones left
2. Board Control is Strategic Power - Maintaining board independence allowed Adventris to reject investor scientific advice and make rapid strategic decisions based on their expertise
3. Founder Mode Evolution - The approach progresses from intensive oversight to partnership-based accountability as teams develop competence and alignment

Actionable Insights:

• Implement accountability structures immediately and expect some team members to self-select out
• Prioritize board control over valuation in funding rounds to maintain strategic decision-making power
• Consult with other founders in your industry to learn specific strategies for retaining control
• Use SAFE structures and avoid priced rounds when possible to delay board seat negotiations
• Focus decisions on core principles (patient benefit and scientific data) rather than investor preferences

Timestamp: [8:00-16:14]