Biotech proved a surprisingly bright spot in 2022’s startup correction

No startup sector was entirely immune from the 2022’s market uncertainty — except maybe AI — but some proved more resilient than others. Biotech was one of the most fortunate.

The sector recorded 1,054 U.S.-based deals in 2022, worth a collective $30.7 billion, according to Pitchbook data. Those figures fell short of the 1,415 biotech deals struck in 2021 worth a total of $39 billion. But the declines were not the worst we found: Biotech showed a more modest year-over-year decline in investment volume (21%) than many other sectors including fintech (37.7%), consumer tech (53%) and enterprise tech (33%).

Comparing any sector’s results to 2021 is slightly specious, as that year was the peak of the last startup boom. Compared to 2020’s more conservative 1,143 biotech deals worth $29.6 billion, last year wrapped up on par.

U.S. biotech deals also set new records in 2022 for both median deal size, $33.5 million, and median valuation, $38 million.

Biotech investors told TechCrunch that while they definitely felt the squeeze of the overall economic conditions last year — and noticed tourist investors shying away from the category, similar to other sectors — many weren’t surprised that the category performed better than some of the other more buzzy industries for a few key reasons.

Biotech proved a surprisingly bright spot in 2022’s startup correction by Rebecca Szkutak originally published on TechCrunch

6 investors discuss why AI is more than just a buzzword in biotech

As ChatGPT has so aptly demonstrated, AI is now truly entering the mainstream consciousness. That’s why we weren’t very surprised when a slew of investors told us they rarely see a biotech startup that doesn’t incorporate AI in some form or other these days.

“Most of the companies we have seen have an AI component to support the discovery or development processes,” Francisco Dopazo, a general partner at Humboldt Fund told TechCrunch recently.

But despite becoming quite the buzzword, AI’s apparent ubiquity in biotech isn’t actually driving deal flow or higher valuations. So to get a better idea of how AI is affecting biotech in 2022, we asked six investors to tell us what they look for in a biotech startup today.

For Franck Lescure, a partner at Elaia Partners, in biotech, having an AI component isn’t an automatic deal closer. “We do not favor biotech startups with extant AI over those without: Bio-revolution is not only digital. Digital is one tool; the other major tool is the living organism,” he said.

VCs are also increasingly looking for what biotech startups can do with AI beyond just R&D, and are wary of companies that use the technology as a marketing tool.

“When evaluating ‘AI for drug discovery companies,’ I view AI as a tool,” Shaq Vayda, principal at Lux Capital, told TechCrunch. “Much like how any modern biotech company is using the latest and greatest tools, AI is becoming more and more common as part of biotech workflows. The bigger question for investors is getting a better understanding of what exactly AI is attempting to model and predict.”

Also, just because a startup uses AI doesn’t mean it can escape being compared to struggling public biotech comparables. “The public markets are the final arbiters of value, and the valuations coming back to earth this year have begun to flow through to startup funding,” said Sarah Guo, founder of Conviction. “I expect we’ll continue to see some digestion through the next year or two, as many mid-stage companies have built major war chests and don’t yet need to come back to market.”

The survey also covers the implications of U.S sanctions on China for startups in the space, considerations for startups thinking of taking capital from government bodies, how to pitch these investors, and more.

We spoke with:


Robert Mittendorff MD, general partner and head of healthcare, B Capital

The NASDAQ Biotechnology Index peaked in 2021. Have declines in the public-market valuations of biotech companies impacted your investments in the sector?

Public market biotechs are dramatically down as interest rates rise and the focus on near-term development outweighs the promise of longer-term results and approvals. As a result, a significant proportion of biotech companies are trading below cash.

Given the substantial and positive flow of data in the space, we view market sentiment as overly negative. These valuations have affected private-market rounds’ size, pricing and structure. Private biotechs are considering the reprioritization of their assets — deciding whether to partner second or third assets with strategics, and evaluating structure in tranched financings to reach their fundraising targets.

Of the biotech startups you’ve seen lately, how many had an AI component? Do you favor biotech startups with extant AI capabilities over those without?

AI has become a very important part of next-generation drug discovery in both the small molecule and biologics spaces. Boston Consulting Group (BCG) partner Chris Meier reported in the March 22 Issue of Nature Reviews Drug Discovery that 24 “AI native” drug discovery companies have a combined 160 disclosed discovery programs. We are many more above this.

Recently our own portfolio companies Atomwise and InSilico each inked $1.2 billion deals with Sanofi. Still, the majority of biotechs raising capital are not “AI-enabled.” This isn’t a necessary condition for us, but in many spaces, computational approaches can rapidly improve drug discovery success and speed, at a potentially lower cost.

We also see AI being used in the biologics space, although the technology is used there far earlier. AI-enablement doesn’t increase our interest unless the technology is robust, mature and adds value to the platform in a meaningful way.

IBM sold Watson Health to private equity in 2022 after investing billions into it. What can biotech startups and investors learn from what could be seen as a cautionary tale?

Biotech companies will ultimately be measured largely by their therapeutic pipelines and portfolios rather than by their tech platform.

AI for AI’s sake doesn’t hold water anymore. Results, whether in the form of novel therapeutic programs, diagnostic capabilities, or other clinically meaningful outcomes, are necessary.

We know quite a few startups are working on AI-assisted drug or protein discovery. Where else can AI play a role in healthtech?

AI is a capability, or more accurately described as a set of computational capabilities that can be applied to a set of problems where conventional techniques have demonstrable limitations. AI technology can play a role in biologics, small molecules, and even cell therapy.

We have witnessed its application in every aspect of a biopharmaceutical’s business — from discovery, clinical development, and applications in real-world evidence creation to go-to-market motions and post-market patient engagement.

AI is not a monolith; as a set of capabilities, the power of learning systems affords benefits to many previously difficult or intractable problems.

How commercially viable will personalized medicine be in the next five years?

Personalized medicine is already here. See the success in oncology over the last decade, from targeted therapies that are based upon tumor genomics to cell therapies that are N-of-one therapies, where a patient’s own immune cells are engineered to attack the cancer.

Personalized medicine as a viable business has already borne out. The question of how far we can go with personalized therapy is the one being answered in the market today.

Clearly, many therapies do not need hyper-personalization, but as we learn more about cancer, metabolic disease, and neurological disorders, we are enabled with advancements in biologic and computational science to customize or configure therapies for each patient.

Y Combinator welcomed a significant number of healthtech startups in its recent batches. Has YC’s presence had any impact on early-stage valuations? 

Y Combinator has been a net positive force in driving innovative experimentation at the early stages of company development. Their healthtech cohorts are solid, and their apprentice model works well there.

They are still perfecting their approach to projects that focus on biologic science, but I remain optimistic. They have had far less of an effect on valuations for us than the larger momentum firms that recently moved into healthcare over the last few years.

How has due diligence in this space changed in 2022?

We have welcomed the investment environment of 2022 as both companies and venture investors can diligence each other at a more natural pace. Venture capitalists and founders need time in the process of diligence to understand each other, and the fervent environment of 2021 diminished and, in some ways, attempted to commoditize both.

As venture capitalists, we focus on selecting teams and projects that have the highest merit as transformative companies. This exercise takes significant effort and a clear understanding of a number of areas that cannot be accomplished in a day.

Diligence is more efficient now than in 2019, but we have returned to a far healthier pace for both founders and VCs.

Is Big Pharma interacting more with biotech startups this year than in prior years? When approaching yet-private companies in the space, do the majors favor M&A or corporate venture activity?

We are starting to see more deal-related activity pick up, but with a heavy tilt towards business development deals, and some corporate venture activity. Biotech has proven its worth as the engine of innovation for the biopharmaceutical industry, and larger strategics have clear programs for engaging with smaller venture-backed entities.

One would imagine given the valuations we are seeing in the venture-backed ecosystem that more M&A would occur given the quality of many of these assets relative to price, but we are at the early stages of that curve.

We heard that U.S. sanctions on China could extend to biotech. What impact could this have on AI-enabled biotech startups elsewhere?

Clearly, CFIUS continues to have important implications on venture financing across all sectors. Biotech is no different, and there may be more sensitivity moving forward, especially as it relates to advanced technologies, particularly in tech and biology.

This may have a modest cooling effect on the pricing of some assets, but I doubt it will affect whether quality companies and teams are funded properly.

Should AI-enabled biotech startups take non-dilutive capital from government entities? Why or why not?

This is a complex question. If the entity is a U.S. government affiliate, the answer is maybe. For other governments, in particular those outside the U.S. or Europe, it is a more challenging question.

Government funding nearly always has conditions of some kind that have to be clearly balanced with the future path of the company. If the funding is from a military source, the implications of dual-use technologies must be considered, and so must be the strategic drift that such funding might encourage.

Are you open to cold pitches? How can founders reach you? 

Yes, but warm pitches are usually better. You likely have someone in your network who is also in mine. My email is rmittendorff@bcapgroup.com.

James Coates, health and human performance principal, Decisive Point

The NASDAQ Biotechnology Index peaked in 2021. Have declines in public-market valuations of biotech companies impacted startup investment in the sector?

Definitely. Going public is a preferred exit strategy for many, and those valuations have just been cut by more than 80%, driving down demand for all but the highest-quality startups. As evidenced by the XBI itself, such cycles are part of the sector.

Of the biotech startups you’ve seen lately, how many had an AI component? Do you favor biotech startups with extant AI capabilities over those without?

The ubiquity of AI in pitches that I see is striking. It’s hard for a biotech company to convince me they are doing more than just using AI as a component of their R&D (which they probably ought to be!).

IBM sold Watson Health to private equity in 2022 after investing billions into it. What can biotech startups and investors learn from what could be seen as a cautionary tale?

Commercialization and market expansion are not necessarily immediate downstream consequences of innovation for companies.

We know quite a few startups are working on AI-assisted drug or protein discovery. Where else can AI play a role in healthtech?

Anything involving data, be it electronic health records or imaging and image-guided procedures. We’re particularly excited by cognitive neuroscience and human performance in this context.

Y Combinator welcomed a significant number of healthtech startups in its recent batches. Has YC’s presence had any impact on early-stage valuations? 

We work closely with many innovative ecosystems in health and life sciences. None of the investments we are most excited about are from YC (at this time).

How has due diligence in this space changed in 2022?

As I mentioned in my TechCrunch article: cash run-way, non-dilutive capital and market size have reemerged as the key metrics in determining whether or not to invest alongside the science.

Should AI-enabled biotech startups take non-dilutive capital from government entities? Why or why not?

If it aligns with the commercial trajectory of the company, then yes. If the grant or contract doesn’t align with what the company aims to accomplish, they should not take the funding (unless in life support mode!).

Are you open to cold pitches? How can founders reach you?

6 investors discuss why AI is more than just a buzzword in biotech by Anna Heim originally published on TechCrunch

5 ways biotech startups can mitigate risk to grow sustainably in the long run

The unprecedented explosion of investment in life sciences over the past decade has resulted in incredible new therapies for patients, strong financial returns for companies and an overall increase in translational research, which is critical to advancing the next generation of therapies. It has also led to eye-popping levels of capital raised by early-stage companies, some of which were years away from entering the clinic with their first product.

Naturally, a generous flow of financing generates excitement for everyone involved. Capital is the fuel that advances scientific and technological innovation, and it means a life science startup can create products that benefit the world at large.

But what happens when the funding suddenly dries up?

In the world of biotech, for example, it’s extremely capital intensive to develop multiple products that are all going through clinical trials simultaneously. The infrastructure needed to maintain these different programs can be too unwieldy to weather a financial drought.

A better approach would be to focus on a lead program — a single product that they can take through various stages of development, ultimately leading to FDA approval. In fact, lead programs validate the value of an underlying platform, enabling companies to raise capital through licensing and partnerships.

Founders shouldn’t let peer pressure or investor check size mandates dictate their financing strategy.

There will always be ebbs and flows in funding, so here are five ways life science startups can optimize for success regardless of the economic climate.

Don’t confuse successful fundraising with a successful company

At the end of the day, fundraising is a means to an end. The mission for most life science startups is to improve patient outcomes. However, science is hard, and cash in the bank does not overcome the complexities of human biology. Plenty of companies have successfully raised significant amounts of capital but were never successful in developing a beneficial product, therapy or technology.

While not a perfect proxy, the value at which a venture-backed company exits (through M&A or IPO) can be an indication of its success in developing a new product. However, there is practically no correlation between the amount of capital a company raises and its ultimate exit value.

Since 2010, the R-squared between exit value and total invested capital — a measure of how correlated the two variables are — for all healthcare exits is a paltry 0.34. When you drill down to a correlation between the exit value and the amount of capital raised in a company’s Series A financing, it drops to a practically negligible value of 0.05, according to PitchBook.

These statistics support the notion that just because a company raises significant amounts of capital (especially early on), there is no guarantee of a successful investment outcome.

Founders shouldn’t let peer pressure or investor check size mandates dictate their financing strategy. Instead, focus on advancing your program through the key stages of technical and clinical development.

5 ways biotech startups can mitigate risk to grow sustainably in the long run by Ram Iyer originally published on TechCrunch

Form Bio says now is the time to launch — despite cooling software sales

As companies aim to cut costs and reel in spending amid uncertain macroeconomic conditions, Form Bio thinks it is actually the perfect time to launch its platform. The software company was developed at Colossal Biosciences — known for its goal to bring extinct critters like the wooly mammoth back to life — and is now striking out on its own.

The software Form Bio developed is meant to bring a suite of workflow solutions to the computational biology space, which uses data and modeling to understand biological systems and includes sectors like gene therapy and biotech.

The platform will use machine learning to help researchers and companies go from idea to scientific breakthrough faster by simplifying the data analytics processes in between and allowing users to choose from existing workflow templates that can be edited to fit a company’s specific needs.

Form Bio announced it was spinning out of Colossal Biosciences on September 27 with $30 million in funding led by JAZZ Venture Partners and Thomas Tull, both Colossal Biosciences investors.

Kent Wakeford, the co-CEO of both Form Bio and Colossal, said that the idea for Form Bio started on day one of Colossal’s journey when they tried to get started and realized there wasn’t a one-stop software they could use.

Form Bio says now is the time to launch — despite cooling software sales by Rebecca Szkutak originally published on TechCrunch

5 investors explain why longevity tech is a long-term play

Of all the stories passed on through history, the tales of life unending have persisted in the human imagination without much change. The details differ, but nearly every civilization right from the time of the Egyptians has in some form or the other sought to delay death.

While we’re still far away from achieving that lofty goal, science has advanced a lot and as life expectancy increased, longevity is now a realm of technology and medicine that aims to increase how long people can live healthily.

“There is a common misconception in the general public that longevity means being frail and looking old for longer (“Curse of Tithonus”),” said Nathan Cheng and Sebastian Brunemeier of Healthspan Capital. “The goal is to slow the pace of aging, and even reverse the clock — this is possible in animals already. Longevity therapies mean we will live longer and in better health.”


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But the cost and time involved in developing longevity solutions presents a major hurdle, which means founders must be prepared to take the long view. “It is very difficult to convince people to do things that leave a visible impact only in the long term. Longevity is one of those things,” said Samuel Gil, partner at JME Ventures.

“The space is only getting started now and will infiltrate all aspects of our life in the next five to 10 years.” Samuel Gil, partner, JME Ventures

But Gil noted that the sheer breadth of opportunity the space offers is nearly unprecedented:

There are multiple angles to solve problems for very heterogeneous groups with different requirements. Health span versus life span, longevity for pets versus humans, biotech versus wellness, seniors versus young people, dependency versus autonomy, prevention versus treatment, analytics, education, infrastructure … Almost like how fintech was not just about creating credit card startups, we will see longevity APIs, back ends and many others.

It’s becoming clear that longevity as a theme has resonated with investors, though it appears it will be some time before more generalist investors take interest.

To get you up to speed on where the longevity market stands and where it’s headed, we spoke with:


Samuel Gil, partner, JME Ventures

What’s the most important thing first-time longevity founders need to know?

Longevity is a loaded word. Although most people are interested in extending health spans (number of years you live with no major age-related health issues), not everyone is interested in (and some have prejudices against) extending life spans (delaying human death).

There are multiple reasons for this. Some think that life is meaningful because it is finite (who wants to live forever?). Others think about environmental or economic issues.

So my advice here is to use the term “longevity” with caution or use alternatives.

As we all know, it is very difficult to convince people to do things that leave a visible impact only in the long term. Longevity is one of those things. My advice here is that your product has to solve a problem for the user right now — help them relieve back or knee pain, look better and so on — to entice them to buy now. Then, you can use the longevity program as a way to retain the user for the long term.

There are multiple angles to solve problems for very heterogeneous groups with different requirements. Health span versus life span, longevity for pets versus humans, biotech versus wellness, seniors versus young people, dependency versus autonomy, prevention versus treatment, analytics, education, infrastructure … Almost like how fintech was not just about creating credit card startups, we will see longevity APIs, back ends and many others.

Analysts estimate that the market for delaying human death could be worth $610 billion by 2025. What would unlock more growth in this sector?

Let me take the opposite point of view: I think the main challenge of the space is that the most audacious approaches and products have to be clinically tested in large samples of the population for very long periods of time. However, there are many other things that you can already try with a big upside and almost no downside.

As soon as a clinical trial shows positive results in humans, it will be a gold rush.

What are you most enthusiastic about in the longevity space?

We all know how powerful technology can be in shaping behavior. I believe there is enormous potential in using technology for shaping health-positive behavior (sleep, exercise, nutrition) in the population. The impacts on the healthcare system may be tremendous.

I am also very keen on quantified self-movement. I find it very gross that we know in real time what is happening in our cars, but we have no clue what’s going on inside our bodies. Continuous monitoring is going to be a reality at some point.

3 tips for biotech startups seeking non-dilutive capital to survive the downturn

Future-proofing the finances of your biotech startup through a market collapse means more than just raising capital or rushing to close your round.

I perform due diligence on dozens of life science companies each week whose technologies might help future-proof the world against the next biothreat, pandemic or otherwise. I see everything from neural probes and artificial intelligence for clinical trials to synthetic biology and quantum sensors. Every startup coming across my desk was well capitalized, but trouble might be on the horizon.

With inflationary market dynamics now firmly here and fiscal tightening ongoing, it’s natural that more speculative ventures with higher cash burns, such as biotech — especially the deep science stuff — suffer the most and suffer first.

But government investment cycles oppose private investment dynamics. When the economy is doing better, it requires less intervention and support. During times of crisis, monetary and fiscal policies are meant to resolve economic burdens swiftly. This is as true today as it was during the early 2000s or after 2008.

Founders of biotech startups are most vulnerable in these conditions and must look beyond classic fundraising to survive. In a downturn, non-dilutive grants or contracts from the government should be seen as more appealing than ever because they provide runway without dilution and make for great headlines.

As a startup, it’s easy to focus on dilutive capital raises, even if the macroclimate may not be the best for it.

Our team built our venture capital firm through advisory work. Since 2019, we’ve worked with over 100 startups in every sector from across the country, securing them over $350 million to innovate emerging technologies.

We take a broad view of national defense and consider any technology that might help future-proof our way of life, life sciences included. Most founders don’t know it before they engage with us, but there are large pots of non-dilutive capital out there earmarked for applied life science research that have 100% success rates. You just have to know where to look.

So how should you go about sourcing non-dilutive capital from the government for your biotech startup?

Don’t ignore the DOD

We support health startups all the time that aren’t aware of how much life science research and development funding the U.S. Department of Defense has; some of it even dedicated to small businesses.

The Army, Navy and Air Force each have their own strategic health and life science priorities, but so do the Defense Health Agency, Defense Innovation Unit, the Congressionally Directed Medical Research Program, Defense Advanced Research Projects Agency and NASA, just to name a few.

For BioNTech, the COVID-19 vaccine was simply the opening act

BioNTech’s founding story dates back to the late 1990s, when CEO and co-founder Uğur Şahin, his wife and co-founder Özlem Türeci, and the rest of the seven-person founding team began their research.

Focused specifically on an area dubbed “New Technologies,” mRNA stood out as one area with tremendous potential to deliver the team’s ultimate goal: Developing treatments personalized to an individual and their specific ailments, rather than the traditional approach of finding a solution that happens to work generally at the population level.

Şahin, along with Mayfield venture partner Ursheet Parikh, joined us at TechCrunch Disrupt 2021 to discuss the COVID-19 vaccine, his long journey as a founder, what it takes to build a biotech platform company, and what’s coming next from BioNTech and the technologies it’s developing to help prevent other outbreaks and treat today’s deadliest diseases.

“At that time, mRNA was not potent enough,” Şahin recalled. “It was just a weak molecule. But the idea was great, so we invested many years in an academic setting to improve that. And in 2006, we realized ‘Wow, this is now working. Okay, it’s time to initiate a company’.”

In an increasingly hot biotech market, protecting IP is key

After a record year for biotech investment in 2020 — during which the industry saw $28.5 billion invested across 1,073 deals — the market for new innovations remains strong. What’s more, these innovations are increasingly coming to market by way of early-stage startups and/or their scientific founders from academia.

In 2018, for instance, U.S. campuses conducted $79 billion worth of sponsored research, much of it thanks to the federal government. That number spiked amid the pandemic and could increase even more if President Biden’s infrastructure plan, which includes $180 billion to enhance R&D efforts, passes.

Since 1996, 14,000 startups have licensed technology out of those universities, and 67% of licenses were taken by startups or small companies. Meanwhile, the median step-up from seed to Series A is now 2x — higher than all other stages, suggesting that biotech startups are continuing to attract investment at earlier stages.

When it comes to protecting IP, early and consistent communication with investors, tech transfer offices and advisers can make all the difference.

For biotech startups and their founders, these headwinds signal immense promise. But initial funding is only one part of a long journey that (ideally) ends with bringing a product to market. Along the way, founders will need to procure additional investments, develop strategic partnerships and stave off competition. All of which starts by protecting the fundamental asset of any biotech company: its intellectual property.

Here are three key considerations for startups and founders as they get started.

Start with an option agreement

Most early-stage biotechnology starts in a university lab. Then, a disclosure is made with the university’s tech transfer office and a patent is filed with the hopes that the product can be taken out into the market (by, for instance, a new startup). More often than not, the vehicle to do this is a licensing agreement.

A licensing agreement is important because it shows investors the company has exclusive access to the technology in question. This in turn allows them to attract the investments required to truly grow the company: hire a team, build strategic partnerships and conduct additional studies.

But that doesn’t mean jumping right to a full-blown licensing agreement is the best way to start. An option agreement is often the better move.

In an increasingly hot biotech market, protecting IP is key

After a record year for biotech investment in 2020 — during which the industry saw $28.5 billion invested across 1,073 deals — the market for new innovations remains strong. What’s more, these innovations are increasingly coming to market by way of early-stage startups and/or their scientific founders from academia.

In 2018, for instance, U.S. campuses conducted $79 billion worth of sponsored research, much of it thanks to the federal government. That number spiked amid the pandemic and could increase even more if President Biden’s infrastructure plan, which includes $180 billion to enhance R&D efforts, passes.

Since 1996, 14,000 startups have licensed technology out of those universities, and 67% of licenses were taken by startups or small companies. Meanwhile, the median step-up from seed to Series A is now 2x — higher than all other stages, suggesting that biotech startups are continuing to attract investment at earlier stages.

When it comes to protecting IP, early and consistent communication with investors, tech transfer offices and advisers can make all the difference.

For biotech startups and their founders, these headwinds signal immense promise. But initial funding is only one part of a long journey that (ideally) ends with bringing a product to market. Along the way, founders will need to procure additional investments, develop strategic partnerships and stave off competition. All of which starts by protecting the fundamental asset of any biotech company: its intellectual property.

Here are three key considerations for startups and founders as they get started.

Start with an option agreement

Most early-stage biotechnology starts in a university lab. Then, a disclosure is made with the university’s tech transfer office and a patent is filed with the hopes that the product can be taken out into the market (by, for instance, a new startup). More often than not, the vehicle to do this is a licensing agreement.

A licensing agreement is important because it shows investors the company has exclusive access to the technology in question. This in turn allows them to attract the investments required to truly grow the company: hire a team, build strategic partnerships and conduct additional studies.

But that doesn’t mean jumping right to a full-blown licensing agreement is the best way to start. An option agreement is often the better move.