The Q2 2019 initial public offerings (IPOs) market has heated up after a Q1 2019 slowdown partially driven by the longest government shutdown in U.S. history. Ernst and Young reported that 205 IPOs were executed in 2018 on the New York Stock Exchange (NYSE) and Nasdaq, raising almost $53 billion of capital. The biotechnology sector was represented well:

EvaluatePharma tabulated 68 biotech IPOs in 2018, raising more than $7 billion of capital. The dramatic increase in biotech capital raised via IPO since 2016 can be seen in Figure 1.

One interesting trend is the substantial increase in the average amount raised per biotech in 2012 ($51 million) compared to 2018 ($105 million). Additionally, the number of $100 million IPOs increased from two in 2012 to 31 in 2018—the previous high was 18 in 2014. While the government shutdown in Q1 2019 momentarily slowed the market, there were still 10 biotech offerings raising more than $1 billion of capital. Three biotech IPOs, led by Gossamer Bio, which raised $317.4 million, each raised more than $100 million. Perhaps most impressive is that the biotech capital raised in 2018 was more than 2016 and 2017 combined.

The impact can be felt across the drug development landscape. Consider the following:

• The number of companies with an active compound in their pipelines increased 53% from 2012 (2,705) to 2018 (4,134), per Pharmaprojects, January 2018;
• Total drugs in development increased 46% from 2012 (10,452) to 2018 (15,267), per Pharmaprojects, January 2018;
• Research and development spend outside of the top 30 pharmaceutical companies represented 37% of total pharmaceutical R&D spend in 2017, up from 28% in 2010, per PivotalFinancialConsulting.com, September 2018; and
• Since 2012, 31 biotech companies have been acquired for potential valuations exceeding $1 billion each and $96 billion in aggregate, per Silicon Valley Bank’s Trends in Healthcare Investments and Exits 2019 and Clinipace market intelligence.

Why all the investor interest in biotech?
Investor interest is usually driven by a return on investment commensurate with the investment vehicle’s risk profile. Biotech companies, and drug development, in general are widely regarded as risky. Financial risk (most biotechs will need to raise additional funds), the length of time required to commercialize, and drug development risk (will the drug be safe and show efficacy) raise complications. Last year, a group at MIT calculated that success rates in drug development were 13.8% across all therapeutic areas. Or, said a different way, the failure rate was greater than 85%.

Figure 2 shows the 10-year compounded annual return on various stock market composites. The S&P Biotech Exchange Traded Fund and the Nasdaq Biotech Index both have annual returns in the 18%-19%—not far off the Nasdaq 100 Technology Sector Index. The return premium for the increased risk is pretty healthy when compared to the Dow Jones Industrial Average (DJIA) and the S&P 500 Index, both at 12.3%. 


In addition to examining biotech returns historically, it is worthwhile to see how the most recent batch of biotech IPOs has fared. The analysis in Figure 3 is based on data available at Nasdaq.com and IPOScoop.com and includes biotech IPOs from March 2018 through February 2019, with the original IPO price along with the April 19, 2019, closing price. A few caveats: This list excludes secondary offerings; there may be a few expected IPOs missing. Also, because these were provided by the sites, a few IPOs or microcap companies may not have been included.


A few observations from the data:

• 60 companies raised over $6.4 billion of capital with a current return of 0.1%—thus, an investor would currently have broken even with this stock portfolio;
• 33 (55%) companies are currently below their IPO price; and
• While the portfolio is stable, there is wild variability among the group: 11 companies have lost 50% of more from the original IPO price; 22 companies have lost between 1% and 50% from the original IPO price; 19 companies have gained up to 50%; 5 have gained between 50%-75%; and 3 have gained more than 100% of value.

It appears that biotech investing should be pursued in accordance with most investment philosophies that recommend a balanced portfolio to manage risk and optimize returns. However, it is also clear that while a balanced portfolio can result in strong gains against the DIJA and the S&P, investments in the right companies can result in once-in-a-lifetime returns.

The information in Figure 4 was taken from Silicon Valley Bank’s (SVB) “Trends in Healthcare Investments and Exits 2019” combined with research from Clinipace’s market intelligence team. The companies included have been dubbed “unicorns” by SVB because of their outsized returns—typically earning valuations exceeding $1 billion early in their evolution. The investments have been categorized as M&A (merger and acquisition) and IPO successes. The total valuation between the two groups is almost $93 billion. Some of these deals include potential milestone values to be achieved; if those  aren’t realized, then valuations could drop.


Analyzing the data uncovers several key data points:

• Companies with a focus on immuno-oncology and oncology dominate with almost $66 billion (71%) of the total returns;
• Companies with an immunotherapy, gene, or cell therapy technology garnered almost $47 billion; and
• The biotech community has become a source of R&D for large pharma, which completed a majority of the acquisitions.

Are biotechs still attractive investments?
Positive historical investment returns do not guarantee future successful returns. What makes the biotech sector such an appealing investment in 2019?

Oncology
The worldwide market for cancer drugs is estimated at $133 billion and expected to reach $200 billion by 2022, averaging 10–13% growth over the next five years, with the U.S. market reaching as much as $100 billion by 2022, averaging 12–15% growth, according to the IQVIA Institute for Human Data Science. According to some estimates, 30% of the revenue growth in the pharma industry will come from oncology, and probably nine of the top 20 products in 2024 will be oncology products.

Immuno-oncology
GlobalData estimates that the total immuno-oncology market will be worth approximately $14 billion in 2019 and $34 billion by 2024. Checkpoint inhibitors will drive the growth, growing from $10 billion in 2019 to $24 billion by 2024. Per IQVIA, the pipeline of immunotherapies is particularly active and includes almost 300 molecules with 60 separate mechanisms being evaluated in Phase I or Phase II clinical trials, which is a significant jump from the four mechanisms in Phase III trials or under regulatory review. These immunotherapy trials are being conducted across 34 different tumor types, indicating the broad-based application of this new approach to cancer treatment.

Gene Therapy
Per Allied Market Research, the global gene therapy market was valued at $584 million in 2016 and is estimated to reach $4.402 billion by 2023, registering a CAGR of 33.3% from 2017 to 2023. Manufacturers are also preparing for growth in this market. In April 2019, Catalent announced it would buy privately held Paragon Bioservices for $1.2 billion in cash, bolstering its capabilities to make gene therapy drugs for its biotech clients. Evercore ISI analyst Ross Muken said the M&A activity is likely to continue and expects contract manufacturers to expand their gene therapy capabilities due to the potential of these treatments to drive the next major leg of industry growth.

FDA Approvals Increase
The FDA’s current progressive approach to drug development is challenging the industry to develop novel approaches to clinical trial design and execution. While it remains to be seen if the new FDA commissioner will maintain this emphasis, recent trends have been positive. 2018 was a record year for new drug approvals (NDA) with 59. Perhaps even more important for the biotech sector is that 34 NDAs in 2018 came from companies outside Scrip’s list of the largest pharma/biotech companies based on revenue—a welcome statistic showing that increased investment is translating into more approved drugs.

Failures
Success and failure in drug development go hand in hand. Several of the unicorns previously mentioned have not panned out as expected.

AbbVie had to write off about $4 billion for Stemcentrx following a Phase III study of Rovalpituzumab Tesirine (Rova-T) that had an overall shorter survival in the Rova-T arm. This is disappointing as Stemcentrx could have been worth as much as $10 billion had Rova-T been successful as a second-line therapy for advanced small-cell lung cancer.

Late last year, Gilead took an $820 million impairment charge on its Kite Pharma acquisition because of the failure of KITE 585, which is one of four CAR-T assets in Kite’s pipeline that was undergoing a Phase I trial for multiple myeloma. Gilead chose to discontinue development due to sub-par efficacy data. Analysts have speculated that Gilead may have significant future impairment charges related to Kite.

Johnson & Johnson abandoned development of AL-8176 (lumicitabine), an anti-RSV drug, wiping $900 million off the value of the assets it acquired from Alios Biopharma. This comes months after J&J took a $630 million hit tied to the suspension of clinical development of AL-8176.

The aforementioned examples put the reward and risk of drug development on display. In some cases, biotechs that were great investments for some investors became poor investments for future acquirers—all within a matter of a few years.

Will interest in biotechs continue?
While nothing is certain, a strong case can be made that interest in biotechs will remain bullish.

Market demand and growth trends
Deloitte’s “2019 Global Life Sciences Outlook” indicates that worldwide prescription drug sales are expected to rise from $900 billion in 2019 to $1.2 trillion by 2024. From 2018 to 2024, the compounded annual growth rate for pharmaceutical drugs is expected to be 6.4%, or six times the 1.2% over 2011–2017.

Strong demand to improve health care
Global life expectancy trends are rising rapidly and expected to reach 74.4 years by 2022, up from 73.3 in 2017. Additionally, the demand for new novel therapies that address unmet needs and for improved access to better medicines will increase. Lastly, while it is estimated that $19 billion of prescription sales may be at risk due to patent expiries, with approximately half resulting in lost sales, these sales are expected to be made up with new therapeutics.

Historical trend of favorable returns
It is hard to argue with 18% compounded annual returns over the past decade. There are not many other sectors where investors can find that consistency and performance over that many years.

Potential headwinds
Factors that could result in depressed investor enthusiasm for biotechs would be:

• A greater number of large post-acquisition or post-IPO biotech challenges could decrease overall valuations and spook investors;
• While the 10-year U.S. Treasury rate has been less than 4% for the past 10 years, a material rate increase over time could impact the amount of money available for investment or change the risk/reward profiles of investors; and
• A slowdown in the IPO market could reduce the fundraising abilities of biotechs.

Overall impact
Biotechnology companies are vital to both the overall economy and improved patient outcomes. According to the Biotechnology Innovation Organization, the U.S. bioscience industry directly employed 1.74 million in 2016, added 273,000 U.S. jobs since 2001, and makes a $2 trillion overall impact to the U.S economy. A quick tabulation of publicly traded biotech stocks (using Yahoo.com’s stock screener) shows over $680 billion of market cap value. Lastly, between 2014-2018, the FDA approved 94 drugs from companies outside the Scrip’s top 100.

These numbers speak for themselves. The biotech sector has made a positive impact for patients, investors, and the economy. This strong performance historically, coupled with the expected rise in prescription drug sales and a continually increasing demand for health care innovations, provides a good reason for optimism for biotech’s future.

*Note: Figure 3 is available for view in the online version of this article at ContractPharma.com

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Jason Monteleone joined Clinipace in October 2017, bringing extensive expertise in the midsized clinical research organization (CRO) sector. A recognized health care and life science leader with more than 20 years of experience, he accepted the role as CEO after several months of strategic consulting with the company. Prior to Clinipace, Monteleone founded Pivotal Financial Consulting LLC, was executive vice president and chief financial officer of Theorem Clinical Research, was chief financial officer of Omnicare Clinical Research and held executive finance positions at MDS Pharma Services and VIASYS Healthcare.