Tumors, Hurricanes & Our First $250K

Despite delays and close calls, our animal trial testing NVN-1 for pancreatic cancer yielded positive data. We also raised $250,000.

I haven’t posted an update since June so I’m excited to write about what we’ve been doing all summer at General Biotechnologies and Nivien Therapeutics.

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www.nivientherapeutics.com

My primary goal with these posts is to provide a perspective on what it’s like to start a biotech company in college. Unlike ubiquitous stories about student-entrepreneurship in software and tech, when I began seriously working on this project last winter there wasn’t much out there about how to do this or what to expect.

I’ll focus on our lead program Nivien Therapeutics in this post and follow up about our exciting secondary program, our experience at MassChallenge and our overarching vision for General Biotechnologies. I’ll also write about pitching VCs in Boston vs. SF and a cool digital health startup we funded at Dorm Room Fund over the summer. (FYI, the application for new investment partners opens Sept. 15th—message me if you’re interested.)

So, how’s Nivien?

To recap, Nivien is a new platform to enhance therapies for treatment-resistant cancers. Nivien candidates target a previously-unaddressed biochemical pathway that plays a key role in determining how well existing therapies perform against various tumor types.

Over the summer, we tested the effectiveness of the front-line chemotherapy for pancreatic cancer on its own vs. in combination with our first platform candidate (NVN-1) in two cohorts of mice with xenograft tumors. We also had a third cohort of mice that received no treatment, which died early in the study.

The front-line chemo, which typically fails within weeks when used against pancreatic cancer, unexpectedly prevented tumor growth for two months in both of our remaining cohorts. As a result, we couldn’t draw any conclusions about the benefits of NVN-1 (or lack thereof) until the chemo failed. That’s when we’d either see growth in the chemo-only cohort while the chemo + NVN-1 cohort remained stable (a positive result), or increased tumor volume in both cohorts (a negative result).

In mid-August, we were weeks past our original end-date and still faced ambiguous results due to the strong performance of the chemotherapy. We’d exhausted our funding from competitions in the spring and had begun paying out-of-pocket to keep the study going. We’d also pushed back our entire preclinical timeline, with no indication of when the front-line chemo would fail. While that would be an amazing problem to have in a clinical trial with human patients, it’s a tough spot for a preclinical oncology startup.

As NVN-1 had not caused side effects in the mice at our initial dosage, we decided to quadruple the concentration. We also reduced the chemo dose by a third in both cohorts to accelerate its failure. At the lower dose, the chemo did stop working and the lines separated nicely over two weeks, with limited cancer growth in the chemo + NVN-1 cohort while the chemo-only cohort experienced an immediate spike in tumor volume.

Then Hurricane Harvey hit Texas.

It turns out that our contract manufacturer — which synthesizes NVN-1 and ships it to the lab in Massachusetts that runs our animal trial — is based in Houston. They sent us an email: all shipments halted indefinitely.

We were already low on supplies because the trial had gone weeks beyond its budgeted end date. We suddenly faced a tough decision. We could express-order NVN-1 from a new manufacturer, but changing the source of an experimental compound mid-trial is a big no-no, with good reason. We could also return to the lower dose of NVN-1, which might mean losing our positive data, or invalidating the results altogether if we ran out of the compound before our partner recovered.

We decided to contract with a New Jersey-based manufacturer that could deliver a new batch of NVN-1 in time for the following week of dosing. Ironically, this company had once temporarily ceased its own operations during Hurricane Sandy in 2012. We’ve learned a valuable lesson: plan for the worst — even freak hurricanes.

With two weeks left before we have complete data, we’ve altered the doses of both chemo and NVN-1 as well as the source of our compound. Therefore, while the results will certainly inform our next steps, we’re not going to weight the final outcome too heavily.

The one decent conclusion we can draw from the trial is that NVN-1 is probably safe in mammals. Our mice have received concentrations 20-fold higher than what we’d ever administer to human patients, with no adverse effects. Fortunately, we also now have the money to run better trials and additional experiments.

A week before Hurricane Harvey shut down our partner, we accepted a $250,000 investment in Nivien Therapeutics from IndieBio and SOSV.

IndieBio is the largest seed-stage biotech accelerator. Starting this winter, Nivien Therapeutics will join the IndieBio labs in downtown San Francisco.

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IndieBio is similar to Y Combinator, but focuses on life sciences and invests twice as much for comparable equity. However, as the IndieBio Accelerator runs from early December to mid-April, I’ll be leaving Harvard just one semester before graduation.

More significant than its impact on my college plans, this funding means we can continue to develop the Nivien platform regardless of the flaws in our first animal trial. It will take more time and money to get Nivien to the clinic, but our partnership with an oncologist at MGH to treat late-stage pancreatic cancer patients following IND approval is already established.

Summertime

It wasn’t all work and no play. The startup grind is as stressful and exhilarating as they tell you it will be, so it was important to get away from it all a couple times.

First, I finally had the chance to finish Barry Werth’s two-book series on the difficult but extraordinary rise of Vertex Pharmaceuticals, which he chronicles in “The Billion Dollar Molecule” and “The Antidote.” I also visited Colombia with my girlfriend and spent a week in Mykonos with a group of friends from Europe. I practiced lacrosse with my 14-year old brother, Bizu, who just got recruited to play ball at The Gunnery, and took a lot of calls from the beach with my 1-year old chocolate lab, Bear.

I miss all of that now that I’m back at Harvard for what could be — if everything goes really well — my last semester of college. But it’s been great to catch up with my friends, many of whom have been working on their own exciting projects, and I look forward to finding out what’s next.

— NBH

This post is part of a series of short essays about student entrepreneurship, VC, and translating scientific research into applied technologies. If you enjoyed reading this post check out the others below and feel free to get in touch!

Update: Nivien closed after 2 years. Read our story in The Washington Post.

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