The Dutch biotech startup Lava Therapeutics launched onto the Nasdaq stock market last week with an €85.6M ($100.5M) IPO. This is a sign of mounting investor interest in cancer treatments based on immune cells known as gamma delta T cells.
The proceeds of the IPO will be used to drive the development of the company’s pipeline of bispecific antibody drugs, which are designed to treat cancer by recruiting a rare type of immune T cells called gamma delta T cells.
Lava’s stock market debut occurs against a backdrop where biotech companies have been rushing to the Nasdaq in droves over the past year. Since its foundation in 2016, the company has raised substantial capital in private funding rounds, most recently a €71M Series C round in September. This is especially high for a company whose lead product candidate will only enter clinical trials this year.
Lava Therapeutics has also attracted the interest of big pharma, making a deal last year with Janssen Biotech – a Johnson & Johnson company – to discover and develop new bispecific antibodies to treat cancer.
One of the main targets of immuno-oncology therapies is cancer-busting alpha beta T cells, which make up the majority of immune T cells. However, an emerging niche focuses on the less common gamma delta T cells. A major advantage of deploying gamma delta T cells in cancer treatments is that they can detect and destroy a wider range of cancerous cells than their more common counterparts.
“We’ve known for a long time that gamma delta T cells have potent anti-microbial and tumor-killing functions, but they also play by very different rules to the other major lymphocyte types in human blood and tissues, so it has been quite challenging to exploit these features for patient treatment,” said Neil McCarthy, an immunology lecturer at Barts and The London School of Medicine, who has no involvement with Lava Therapeutics.
“Excitingly, our understanding of the molecules and mechanisms that control gamma delta T-cell activity has progressed very rapidly in recent years, so we are now far better placed to harness this biology for potential therapeutic purposes.”
There are several drugs already in routine clinical use that are known to activate these immune cells indirectly, such as zoledronate and pamidronate. “It’s not surprising that more precise targeting of these cells has become a hot topic in immunotherapy,”McCarthy added.
The antibodies employed by Lava Therapeutics redirect the patient’s own gamma delta T cells and other immune cells such as natural killer cells towards tumor targets. The company’s lead product candidate draws immune cells, including gamma delta T cells, towards an antigen known as CD1d. This antigen is present on cancer cells in many types of blood cancer, including multiple myeloma, chronic lymphocytic leukemia, and acute myeloid leukemia.
Lava Therapeutics is by no means the only one to explore the use of gamma-delta T cells against cancer. UK firms Adaptate, TC BioPharm and GammaDelta Therapeutics, Netherlands-based Gadeta, and US company In8bio are also attempting to get a slice of the action. They use a variety of approaches that include genetically modifying the patient’s own gamma delta T cells or using donor-derived cells.
Indeed, In8bio looked set to raise its profile further and filed for a €73M ($86M) IPO in October last year. However, the company revised down and then postponed its IPO plans in November, with the reason undisclosed.
Nonetheless, Stefan Luzi, a partner at European investors Gilde Healthcare — which became a lead investor in Lava’s first €16M institutional investment round in 2018 — retains a strong belief in Lava’s approach.
“A key advantage of Lava’s gamma delta T cell-engaging antibodies would be that they are ‘off-the-shelf’ therapies, usable by any patient,” he explained. In contrast, companies that grow the patient’s own immune cells outside of the body and reinfuse them face a process that “is technically complex, involves the disruption of complex biology, and involves delays in delivering the therapy to patients.”
“Lava has demonstrated compelling preclinical efficacy and safety of their candidate molecules in preclinical studies,” said Nanna Lüneborg, a partner at Novo Ventures, which co-led Lava’s Series C financing.
“We see a lot of interest in bispecific molecules in general. Lava has a very differentiated platform, which has allowed it to generate compelling candidate molecules now moving into the clinic, as well as the potential to develop a broad pipeline of additional bispecific molecules.”
The use of gamma delta T cells in immuno-oncology faces several technical challenges, according to McCarthy. One is keeping these cells circulating in the blood for long enough to maximize their contact with blood cancer targets. Another is ensuring that these therapies don’t cause problematic inflammation in organs including the skin, lung, and gut. On the flip side, though, gamma delta T cells could have a lot of potential in future treatments for infectious or inflammatory conditions.
“As we continue to develop better tools able to modify gamma delta T-cell biology in a more targeted way, I am optimistic that these approaches will yield effective new therapies for a range of major disorders,” said McCarthy.
Cover image from Elena Resko