Conviction stock-picking drives biotech success: a biotech market review of 2024

In our last review mid-2024 we had been asking the question: “Are there signs of a biotech market breakout?”. Especially compared to the period between 2021 to 2023, now referred to as the "Biotech Bear Market", or even the "Biotech Nuclear Winter" by those in the industry, the overall biotech market had a decent year, returning 11.3% in AUD for calendar year 2024.

While it was a recovery and consolidation year in general, HB Biotech portfolios had a true breakout year, returning on average 40% over the same period, with much of this outperformance coming in the second half of 2024. In delivering this result, we were reminded that it is increasingly a stockpickers market where it pays to maintain conviction in well researched positions.

Progress rarely occurs in a straight line

While 2024 was certainly a more conducive environment for biotech investment, with inflationary forces being wrestled back to more manageable levels by central banks, progress was far from a straight line throughout the year.

During the first quarter of 2024, biotech investors continued to rejoice that inflation appeared to be coming under control and looked forward to the prospect of future rate cuts by central banks. However the reality that the fight against inflation may be more protracted than investors had hoped for led to a significant reversal in the second quarter of 2024. 

Despite this, while investors were constantly checking the rearview mirror for signs of inflation persisting, the biotech market, overall, was able to enjoy a year of reacting mainly to fundamentals: Data readouts and commercial drug / device launches, as opposed to (over)reacting to comments from central bankers – a welcome change to the environment of 2022 and 2023 where 'macro had its hand on the tiller'.

Despite only a modest gain of 1.7% over the December quarter, the biotech market was far from dull with the biggest market moves resulting from the US Presidential election in November 2024. Markets in general reacted favourably to the Trump presential win, with the biotech market in particular rallying ~5%. However this was quickly wiped out, with interest, due to the controversial appointment of notable vaccine sceptic, Robert F Kennedy Jr (RFK) as Secretary of the Human and Health Services (HHS), which governs the Food and Drug Administration (FDA). 

This initially caused much alarm to the biotech investment community due to concerns about potentially major changes to how the FDA would operate to approve drugs in the US. Resultingly, within the space of a week, 12% had been wiped off the biotech index. 

This drawdown was reversed as a Dr Martin Makary was appointed head of the FDA, largely seen as a sensible pick, known for his pragmatic approach and criticism of inefficiencies in healthcare – in particular the role that Group Purchasing Organisations (GPOs) and Pharmaceutical Benefits Managers (PBMs) play to inflate drug prices in the US. The end result for the election month, November, was a 1% increase for the biotech market – but it was hardly in a straight line.

Given the upfront investment to bring a drug to market is in the range of ~US$2 billion over 7-10 years, biotech drug developers require a degree of certainty that the FDA approval goalposts will not change significantly during this timeframe. Here at HB Biotech we are cautiously optimistic that there will be few major changes to how the FDA operates, and welcome any efficiency improvements. However, we will still likely stay clear of vaccine developers…

With a more conducive investment environment, it therefore comes as no surprise that Biopharma financing in 2024 was the highest since the inflation-driven bear market of 2022 – 2023, however IPOs remained well below pre-COVID levels. With fewer biotech companies going public, it is little surprise that venture financing continued to be strong throughout 2024 as private companies sought further capital to stay private for longer.  

The financing trend that continued was the popularity of "Private Investment in Public Equity" (PIPE). One of the reasons for the increased popularity of this financing methods for US-listed biotech companies, in particular, is that it represents a less costly and more efficient method for listed companies to raise capital from experienced investors. However, on the other hand, they have also been accused of being a form of legalised insider trading, leaving generalist retail investors frozen out of lucrative financing deals.

M&A also continued in 2024, although not at the same pace as 2023, and continued the trend of more numerous, smaller acquisitions with fewer mega-deals that were more common historically. Notable, also, was the high level of private biotechnology company acquisitions in 2024 than in any previous year outside of 2021 (which we treat as an anomalous COVID-related year in any case).

While our portfolios experienced 'only' one acquisition in 2024, as Sanofi acquired Inhibrx Inc for US$2b in May 2024 this continues our average of one portfolio company acquired per year (out of an average of 18 held) since HB Biotechnology was launched.

2024 continues our average of one portfolio company acquired per year (out of an average of 18 held) since HB Biotechnology was launched. 

While the timing and targets of M&A are hard to predict, we continue to believe our portfolios have numerous near-term potential M&A targets.

With a looming Loss of Exclusivity cliff approaching many large pharma blockbuster drugs, we would not be surprised to see M&A increase in 2025. Indeed, as the annual JP Morgan healthcare conference commenced this week, one of the big topics for large pharma CEOs were their plans for the upcoming patent cliff. Also coinciding with JPM were acquisition announcements, the most significant being Johnson & Johnson announcing their $14b acquisition of Intra-Cellular Therapeutics, a bet on neuroscience and gaining the rights to soon-to-be blockbuster Caplyta, a drug which is poised to become the new standard of care for schizophrenia, bipolar and major depressive disorders.

Key themes from 2024

Obesity…

We could hardly do a full year review without mentioning Obesity medications. Continuing the trend from 2022 and 2023, the rise of obesity medications continued to dominate headlines. It is staggering to consider that current market heavyweights, Novo Nordisk (NASDAQ: NVO, makers of Wegovy / Ozempic) and Eli Lilly (NASDAQ: LLY, makers of Zepbound / Mounjaro) have added ~US$1T of market capitalisation between them from 2021 to 2024.

However, the appeal of these drugs is not just cosmetic. Arguably, the start of their real market advance came in late 2022 when long term studies showed evidence that the GLP-1 drug class led to reduced incidence of Major Adverse Cardiac Events (MACE) – a key criteria for insurers to cover the expensive injectable medication for weight loss. Since then, GLP-1 agonists have been, or are currently being studied in indications ranging from Kidney Disease, Sleep Apnoea, Metabolic Associated Steatohepatitis (MASH, formerly NASH) and even Alzheimer's Disease, among others, with many of these studies are due to read out in the next 12-24 months.

While there are many molecules in various stages of development, investment exposure to the GLP-1 class principally continues to be a large-cap pharma game. Here at HB Biotech, where our mandate is to invest in listed drug and device companies with market capitalisation less than US$5b at initial investment, there have been few opportunities to invest in this theme in this small to mid-cap space to date. However, as competitors seek real differentiation the current market incumbents through either novel or complimentary mechanisms of action, as well as pursuing similar, or even superior, efficacy and tolerability through a convenient oral route of administration, we are actively tracking several investment opportunities that meet our investment mandate.

Artificial Intelligence: More evolution than revolution

Major markets have certainly been buoyed by the promise of AI to increase our overall productivity, and consequently the profit margins of corporates. Drug Development has not been immune to the AI craze and it wouldn't take much to find commentary online about how AI is going to significantly cut the time and cost of developing drugs. However, in drug development, we are constantly reminded about how "the more we know, the more we don't know", meaning that there is still so much about human biology that is currently unknown that it is virtually impossible to separate computational models from the wet lab. In other words, any dataset that an AI-algorithm is trained on is likely incomplete and the output needs to be tested in real biological systems – and for drug development, that ultimately means still having to run lengthy clinical trials.

The reality is that AI / ML has been used in drug development for many years now and is already established as a valuable tool to assist in the drug development process. As one researcher explained, the impact of AI is likely to be "more evolution than revolution". I am reminded of attending a briefing by "AI Company" Shrödinger (NASDAQ: SDGR) in New York in 2023 at the initial height of the AI craze where CEO,  Ramy Farid, explained that investors can label them an "AI company" if they wanted, however they have been using machine learning to refine their physics-based algorithms for decades.  Sure, computing speeds are getting faster, but the journey has been incremental - not an overnight revolution.

Indeed, many HB Biotechnology portfolio companies such as Ideaya (NASDAQ: IDYA), Monte Rosa Therapeutics (NASDAQ: GLUE) and Kymera  (NASDAQ: KYMR), routinely utilise AI as a drug development tool, however all would stop far short of calling themselves an "AI Company".

The rise of Chinese innovation

One of the key themes to emerge from 2024 was the rise of China as a source of innovation for the Biopharma industry. Historically assets developed in and data out of China were generally treated with much scepticism. Nevertheless, increasingly both large and small biopharma companies have in-licensed or outright acquired Chinese assets or companies.

As an example, in January 2023 Summit Therapeutics (NASDAQ: SMMT) in-licensed a PD-1/VEGF bispecific antibody, Ivonescimab, for the treatment of late-stage non-small cell lung cancer (NSCLC) from Chinese company, Akeso. When at ASCO in 2024, despite all the clinical trial data having been derived solely from Chinese sites, Summit presented compelling head to head clinical trials results of Ivonescimab vs immuno-oncology heavyweight, pembrozolimab (Keytruda), this prompted Keytruda owner, Merck (NYSE: MRK), to in-license a similar PD-1/VEGF bispecific from Chinese company, LaNova Medicines. Similarly, in December 2024 the same large pharma company, Merck, instead of opting to enter the competitive obesity field with the acquisition of a US or EU developed asset, instead acquired to rights to an oral small molecule GLP-1 from Chinese company, Hansoh Pharma.

Immunology

As we had signalled in our mid-year review, we continue to see Immunology drug development as a key area of growth where there are numerous targets that are increasingly being targeted via novel modalities and / or mechanisms of action. Within our portfolios, Kymera Therapeutics, a company pioneering rationally designed protein degraders, has a large focus on I&I indications, with their lead asset KT-474 having been partnered with Sanofi (NYSE: SNY) to treat hidradenitis suppurativa (HS) and atopic dermatitis (AD), among others. Kymera expanded its I&I pipeline in 2024 with KT-621, an oral STAT-6 degrader which, in preclinical studies, demonstrated full inhibition of the IL-4/IL-13 pathway with picomolar potency that was superior to dupilumab (Dupixent), all in a convenient oral form. To put the commercial opportunity in context, Dupixent, marketed by Sanofi / Regeneron is an injectable medicine that is expected to generate ~US$14b in global sales in 2024 with further growth in 2025 with a recent approval in COPD. In the last two weeks both Johnson & Johnson and Gilead in-licenced preclinical STAT-6 inhibitors, further highlighting the commercial interest in this target.  Initial human data from KT-621 is expected in 1H 2025.

What's in store for 2025?

With overall markets such as the S&P500 and ASX200 delivering back to back calendar years of (well) above-average returns, continually re-testing all-time highs, the same cannot be said for healthcare overall, and biotech in particular which is trading only just above pre-Covid levels following the 2021 to 2023 biotech bear market. 

One of the key reasons we established HB Biotechnology as a dedicated investment offering is because of biotechnology's very low correlation to overall markets. While we will never claim to have a crystal ball to know where markets are heading, we are confident that by maintaining our investment discipline, we should continue our long term track record of outperforming the biotech index through a high conviction portfolio of listed, global biotech stocks, and in doing so, provide a valuable source of portfolio diversification with both high risk adjusted returns and a very low correlation to overall markets no matter what 2025, and beyond, may have in store for us.