How today’s biotechs are helping us Stand Up To Cancer
Today – being the second Friday in September – is Stand Up To Cancer Day, as good an opportunity as any to talk about next-generation treatments that are on the verge of making it into clinical practice.
Oncology is a vast field, with many modalities being developed, and myriad indications – which are increasingly defined not just by their bodily location, but by their pathological drivers and genetic signatures.
What treatments, then, have the greatest potential to move the dial in the years ahead? Where does the greatest unmet need remain? And what gives today’s leaders at the forefront of innovation in cancer hope?
To answer these questions, Stephen Adams spoke with a selection of top-level biotech leaders who are advancing a wide range of modalities. Their thoughts are as below.
What oncology innovation has the greatest potential to improve outcomes for cancer patients over the next five years, and why?
“Taking the extraordinary advances we’ve seen with immunotherapy and cell therapy and making them work much more effectively in solid tumours,” said Sam Cobb, founding CEO of Currus Biologics. The Australian biotech is developing a universal bispecific antibody platform to unlock CAR T-cell therapies for the treatment of solid tumours.
CAR T-cells’ very limited efficacy in solid tumours has been a major stumbling block for some years now, and Cobb said the challenge “isn’t simply getting immune cells to recognise a cancer cell.”
“They also need to expand, persist, and remain functional within a very hostile tumour microenvironment (TME), while overcoming tumour heterogeneity and immune suppression,” she added.
While this might sound like mission impossible, Cobb said “increasingly sophisticated approaches” were being advanced to overcome these hurdles, “including engineered and ‘armoured’ cell therapies, in vivo CAR generation and bispecific approaches and therapies designed to actively modify the TME”.
So, there is no shortage of innovation in this area – perhaps unsurprising, given the phenomenal outcomes achieved by CAR-Ts in some blood cancers.
Huge hopes are also being pinned on creating CAR-Ts in vivo, as this method opens up the possibility of “overcoming many of the manufacturing and access challenges of today’s [ex vivo] autologous therapies”, Cobb said.
Such off-the-shelf treatments would also be “a major step forward” for patients, she added.
Meanwhile, Stephan Schann, CSO of Kainova Therapeutics, which is working on breakthrough treatments in immuno-oncology and inflammation, said: “The greatest opportunity lies in biomarker-led, rational immuno-oncology combinations that reshape the TME and restore immune competence, particularly in solid tumours.”
Better understanding was “enabling the design of therapies that more precisely re-engage antitumour activity and improve patient outcomes,” he said.
In fact, improving the TME is something of a theme. Valerie Vanhooren, co-founder and CEO of Ona Therapeutics, developing ADCs and antibody-based therapies for oncology, said: “The biggest opportunity lies in looking beyond the obvious cancer targets and using a deeper understanding of tumour biology and resistance to uncover new therapeutic vulnerabilities. Advances in patient-derived models, multi-omics, and AI are making it increasingly possible to identify the biology that truly drives advanced disease and translate those insights into new treatments.”
But there are other hot approaches, among them radioligands – which Steven Kelly, newly-appointed CEO of Actithera, said “combine molecular precision with the cancer-killing power of radiation”. Their promise has already been hinted at, with success in prostate cancer, but proponents think this is just the tip of the iceberg.
Kelly said: “By designing treatments that clear healthy tissues rapidly, but remain in tumours longer, we have the potential to deliver more effective radiation while reducing toxicity.”
And Rab Prinjha, chief R&D officer at Curve Therapeutics, said targeting critical “nodal cancer cell vulnerabilities” using cyclic-peptide functional antagonists was showing “significant promise”.
“The hope is that by inhibiting these key nodes we can treat a greater range of cancer cells, irrespective of their driver mutations” – a method which may reduce the likelihood of resistance emerging.
“At Curve, we are seeking to do this by moving away from reductionist drug discovery, to screening DNA encoded libraries directly in cancer cells,” he said.
Liam Tremble, principal scientist at AIM-listed Poolbeg Pharma, noted that “we live in an era of breakthroughs” and mentioned new technologies emerging today, such as celmods and menin inhibitors.
What are the biggest unmet needs in cancer remaining today, and what approaches are showing the most promise in addressing them?
Unsurprisingly, aggressive solid tumours top the list in terms of indications. “That remains an obvious area of unmet need,” said Currus’s Cobb.
But unmet need is also reflected in other aspects, she added, such as durability (or, rather, the lack of it) and lack of access to potentially transformative – but prohibitively expensive – medicines.
She said: “We are increasingly good at producing an initial response in many cancers, but too often the tumour adapts, becomes resistant ,or returns.
“Cancer is heterogeneous and constantly evolving, so, the next generation of treatments needs to address not only how we kill tumour cells initially, but how we generate a deeper and more durable anti-tumour response.”
Currus is tackling this problem with a bispecific antibody it calls BEAT, which is intended to enhance immune activation and improve the persistence and function of CAR T-cells in solid tumours.
All those interviewed identified refractory and treatment-resistant cancers as a major unmet need.
Tremble said: “We need to do better at treating patients with refractory and aggressive subtypes. We are almost there, but we haven’t seen as many drugs navigating the regulatory paths as we would have hoped.”
Schann highlighted non- or poor responders to checkpoint inhibitors, arguing: “Approaches that target immune suppressive mechanisms within the tumour microenvironment, including selective targeting of highly suppressive immune populations, such as CCR8+ regulatory T-cells, are among the most promising for expanding the benefits of immunotherapy to patients who currently have limited options.”
Kelly said: “New modalities such as ADCs, T-cell engagers, radioligand therapies, molecular glues, and cancer vaccines offer real promise to deliver more precise, durable treatments with less toxicity.”
On Stand Up to Cancer Day, what gives you the greatest reason for optimism about the future of cancer research and treatment?
Given the fact that aggressive solid tumours are so front of mind, Ona’s Vanhooren fittingly mentioned “the recent results with daraxonrasib in advanced pancreatic cancer” as a “powerful example” of what gave her hope.
Indeed, results presented at ASCO in June, which showed the next-generation RAS inhibitor nearly doubled survival compared to chemotherapy to 13.2 months, prompted a 42-second standing ovation.
Vanhooren commented: “if we can make such meaningful advances in one of the hardest cancers to treat, it shows how much more may now be possible across oncology.”
Tremble said he was heartened by “so many new drug classes emerging” and the “depth of innovation in China.”
“We are seeing more functional cures and cancer patients living healthily into old age,” he said. “It really brings home why this matters.”
Underpinning their optimism is better fundamental understanding of how cancers survive and thrive – and how we can better intervene – with Kelly and Schann both citing deeper biological insight and Cobb saying this was leading to a “sheer breadth of progress”.
Finally, Curve’s Prinjha reflected on how personal experience had made him more hopeful for the future.
“To see my close family, friends, and colleagues happy and thriving, having successfully come through cancer treatments, fills me with joy and optimism,” he said.
Image courtesy of Stand Up To Cancer.
About the author
Stephen Adams has been an associate director at Optimum Strategic Communications, a specialist life science communications agency, for two years. Prior to that he was a health journalist, spending six years at The Daily Telegraph and then a decade at The Mail on Sunday.
