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Sep 15, 2023
By Sierra Brooks
Drugging the Messed Up DNA Packaging Behind Disease – A Conversation with TippingPoint Biosciences

We talked with the founder of TippingPoint Biosciences — Laura Hsieh, CEO — in the basement of IndieBio last week after her company had just been voted “Killer of the Week” by her peers in Batch 14. Each week at IndieBio, the companies in our batch compete based on their top accomplishments just in the previous week as they learn to move at venture speed. Top companies are nominated by the IndieBio SF team, but the winner is ultimately chosen by a voting of their peers within the batch.

Laura’s been on a mission to transform human health for as long as she could talk, but the ‘tipping point’ to create her startup took some time.

[Sierra]: What was the driving force for you to start a company centered around targeting chromatin? 

[Laura]: “My sister had leukemia when I was young so I spent a lot of time in hospitals by her side while she was getting treatments. Her doctors are like my second family – we still keep in touch. The former Director of Pediatrics at Stanford Hospital is even an advisor for TippingPoint. Ever since that time I’ve been on a mission to create something in medicine with a lasting impact on people’s lives.”

[Mohan]: How did this mission transform into a startup instead of say a career in medicine?

[Laura]: “At first becoming a doctor was the plan but I just fell in love with doing research even as an undergrad. I had an epiphany that the only way to effectively treat diseases was to understand the full range of complexities behind them. I became enthralled with the unraveling of DNA and soon I became an expert in chromatin dysfunction, which really is the driving force behind so many diseases.”

[Sierra]: Wow, so you’re pioneering an entirely new avenue towards thinking about and treating disease.

[Laura]: “Everyone is so focused on gene expression they forget to take a step back and look at the whole picture – messed up heterochromatin is often the true driving force and is what we should be targeting to treat the source of many diseases. Forming a focused startup in this space was this perfect opportunity to apply my years of research in chromatin to make a difference in the field of medicine and I had to take it.”

No sleep, no problem: Laura’s secret to running a Killer startup and raising two kids

[Mohan]: You’re able to be a CEO, run long experiments yourself in the lab while you try to recruit scientists, and still have time to be an awesome mom for your two kids – how do you do it all?

[Laura]: “I learned that I only need a solid 2-3 hours of sleep per night to perform at my best. In a pinch I can get by with no sleep at all and function just fine the next day. This natural gift comes in handy so I can fit in all my mom duties and still have time for a full work day once my kids go to sleep!”

[Sierra]: That’s impressive. It explains a bit about why you’ve been able to accomplish so much during the batch.

[Laura]: “I’m not someone who shies away from hard work; I’ve loved the learning curve of becoming an entrepreneur with a science background. My former research advisor, Geeta Narlikar, is a leading expert in the field of chromatin biology and she has been super active in the company so far. She has years of experience recruiting top talent and finding advisors and has really helped build our team.

[Mohan]: You are exemplary of the kind of scientist-founder CEO we love at IndieBio. But we look for constant evolution. Here you’ve gone from working for Geeta as your advisor during your postdoc to rearranging this key relationship so she is essentially working for you and the company. Tell us how that role transformation is going?

[Laura]: Everything’s been really smooth so far. We’re both direct and open communicators and are able to work together really well. Neither of us has a big ego to satisfy. We just want to translate this science into life changing medicine – no messed up chromatin here in our relationship!

Why she was voted Killer this week

Laura’s first therapeutic target is to develop a treatment for a rare pediatric disease – Diffuse Intrinsic Pontine Glioblastomas (DIPG) – a disease directly driven by aberrant chromatin packaging. DIPG is devastatingly fatal with a 0% survival rate within one year of diagnosis. There are currently no effective treatments for DIPG and companies working towards treatment have been unsuccessful at finding ‘hits’ – molecules which can specifically target DIPG in a pre-clinical setting. 

[Laura]: “Last week we got our proprietary high-throughput screen up and running after months of optimization and tested a library of 10,000 novel compounds – we were able to see several small molecule hits in our first screen! The hits targeted DIPG and did not target normal chromatin. This means they have potential to specifically target DIPG without safety issues, which until now has not been shown by any other company.”

TippingPoint is on track to be much more than a one-hit wonder

Aberrant heterochromatin is proven to play a key role in a wide range of cancers, neurodegenerative disorders, and developmental disorders. In parallel to DIPG, Laura is gearing up to apply her unique platform to other intractable cancers, such as gliomas and pancreatic cancer, with much larger numbers of impacted patients facing bleak survival rates.  Her progress towards developing cures for disease with high unmet medical need has already won her a Golden Ticket from Ono Pharmaceutical Co.

The extra time and effort spent to understand the intricacies of all DNA interactions in a diseased cell in the fullest context possible to date, as opposed to the expression of a single gene, is truly paying off for Laura. Through our brief conversation we could really sense her intense focus, persistence and drive towards achieving TippingPoint’s central mission: Pioneering a completely new approach to target cancers and other disease states by targeting the flawed DNA packaging underlying these disease mechanisms. We can’t wait to see how Laura’s journey has progressed the next time we speak. 

Stay tuned for a deep dive into next week’s Killer!