Infinitopes: Preventing Cancer Recurrence

Progress often happens in fits and starts. Or, “gradually and then suddenly,” as Hemingway wrote.

This has been the story of cancer vaccines. Stimulating the immune system to attack cancer cells is not a new idea. In fact, it dates back to the 19th century. A surgeon named Dr. William Coley arrived at this insight when he observed that some cancer patients with existing bacterial infections had dramatically better outcomes.{{infinitopes-fn-1}} Their tumors appeared to dissolve. In response, he began injecting bacteria directly into the tumors of his patients.

Many patients died. Gradually, the idea was refined. Coley started using dead bacteria. As he experimented, Coley documented several extraordinary responses. But the approach remained crude and highly variable. By the 20th century, however, it became more clear that Coley had really been on to something. For example, the Bacillus Calmette–Guérin (BCG) vaccine, originally developed to prevent tuberculosis, proved to dramatically reduce recurrence rates for high-risk bladder cancer patients.

Over time, immunotherapy—the suite of medicines harnessing the immune system to mitigate cancer—has become a mainstay of modern oncology. CAR-T therapies have delivered extraordinary outcomes for patients suffering from blood cancers. Checkpoint inhibitors are truly Nobel-worthy tools for taking the brakes off of anti-cancer T cells. We know that if we engineer a patient’s own T cells or take their brakes off, the impact can be massive.

But the original idea of making a simpler cancer vaccine has become the red-headed stepchild of this new field. This was not for a lack of effort. Many labs and companies have refined the science of searching for anti-cancer antigens. RNA, DNA, peptide, viral, and even whole-cell vaccines have been tried. Historically, the clinic signal has ranged from nonexistent to inconclusive.

And then we saw signs of life—literally. In 2022, Moderna announced that melanoma patients receiving their personalized mRNA cancer vaccine experienced a 44% reduction in the risk that their cancer would recur. The latest data at five years now show a 49% risk reduction. Cancer patients are living longer thanks to COVID-era breakthroughs in vaccine technology.

These results, in combination with encouraging readouts in other studies, drove a resurgence in optimism for cancer vaccines. After decades of R&D, it became clear that we now have the right building blocks to make this vision a reality. As the MSKCC cancer researcher Vinod Balachandran put it, the problem now comes down to finding “the right antigen, the right delivery technology, and the right [clinical] setting.”

Infinitopes, a spin-out from Oxford University, has obsessed over solving this equation. The company’s mantra is: Right Targets, Right Vectors, Right Patients, Right Time. Building on Oxford’s excellence in biomedical research, Infinitopes has developed a world-class platform to tackle each part of this problem.

In less than five years, they have built foundational technology, delivered incredible pre-clinical results, and worked with UK regulators to innovate on trial design. Now is where the rubber meets the road. Infinitopes has initiated first-in-human studies to test if they can make a dent on one of oncology’s biggest challenges: recurrence.

Surgery can be used to remove primary tumors. But cancers frequently recur, regaining mass and ultimately metastasizing. Roughly 70-90% of cancer mortality can be attributed to metastasis. It’s a massive problem.

The goal for ITOP1, Infinitopes’ first clinical program, is to stimulate the immune system to prevent recurrence after surgical resection.

At the end of last year, we co-led a $15.4M financing with Octopus Ventures to help accelerate the company’s platform expansion and entry into the clinic. Here, we’ll share why we believe Infinitopes has the potential to deliver a real breakthrough for cancer care, and what to know about their groundbreaking VISTA trial.

Right Targets: Infinitopes Measures, Competitors Predict

Consider a flu vaccine. You have a genome, as does the virus. These genomes are distinct. Based on what we know about virus biology, we can pick viral proteins to target for vaccine development. When picking an antigen (or multiple) from a viral protein, the main challenge is ensuring that it will deliver a sufficient immune response. Because it is a non-self antigen that originates from a virus, the risk of triggering an immune response against your own cells is low.

This is not true for cancer. A tumor is a pathology of the self. The distance in genomic space between an individual’s genome and their cancer’s genome is small. Because of this, target selection for cancer vaccines is a hard problem. How can you find antigens on the surface of cancer cells that are not also on healthy cells?

A lot of research has gone into predicting the existence of these types of antigens from DNA or RNA sequencing. Instead, Infinitopes tackles this problem with direct cellular measurement. They use state-of-the-art immunopeptidomics to measure what is actually presented on the surface of cancer cells. This data, in combination with genomics and transcriptomics, is piped into a computational workflow with a suite of AI models that can resolve specific cancer antigens with exceptionally high sensitivity. Crucially, these measurements are done with primary tissues collected from patients with the type and stage of disease that Infinitopes aims to treat.

Early in my research career, I cut my teeth on this exact problem. The sophistication and resolution of the Infinitopes approach makes me feel like a Neanderthal.

Right Vectors: Durable Protection With Clinical Simplicity

There are many possible ways to deliver antigens. Different vaccine modalities each have their own advantages and rationale. Infinitopes optimized to solve three primary problems. First, they use an approach with an abundance of existing safety data in humans. Second, the goal is to ensure a robust anti-cancer T cell response. Third, the goal is to be able to deliver this solution at a massive scale with low cost.

During COVID, we saw large-scale deployment of different vaccine technologies on the scale of billions of doses. In a head-to-head comparison between technologies, viral vaccines triggered the most potent T cell responses. In terms of scale and cost, viral vaccines can be manufactured for as low as $3-4 per dose and can be stored in standard refrigerators.

Infinitopes is building on the powerful advantages of this vaccine platform with the guidance of the world’s leading experts. Oxford professors Tess Lambe and Cath Green, who both played critical roles in developing and scaling the Oxford-AstraZeneca COVID-19 vaccine, serve as trusted advisors to Infinitopes.

With their target discovery engine, they can identify cancer antigens that are widely shared between patients, enabling a pipeline of off-the-shelf products. In pre-clinical experiments that have now replicated across multiple distinct labs, their viral vectors deliver potent T cell responses against these antigens that completely prevent the recurrence of tumors.

Right Patients, Right Time

A pre-clinical result is just that. The North Star for a clinical-stage biotech is to replicate their experimental findings in human patients. But a major challenge—especially in oncology—is that clinical studies often select for the sickest patients with the lowest likelihood of responding. This partially explains why clinical success rates in oncology are lower than for all other therapeutic areas.

A growing percentage of early immunotherapy trials are happening in China, where new regulations enable faster and more flexible enrollment of patients that are less heavily pre-treated than their Western counterparts. The U.K., where Infinitopes is headquartered, has also established infrastructure to support new trials. After the incredible speed of clinical development during COVID, the U.K. launched the Innovative Licensing and Access Pathway (ILAP) to help achieve similar breakthroughs moving forward.

Infinitopes moved quickly and became one of the earliest beneficiaries of this new pathway. Throughout their trial design, they have been able to work hand-in-hand with regulators to design a study that should give patients the greatest chance to benefit from their new medicine. These efforts culminated in the VISTA Phase 1/2a trial, which is already enrolling across three leading U.K. cancer centers.

With a new medicine, the foremost concern is safety. After a Phase 1 lead-in, a subsequent 2a study is designed to give an initial signal as to whether or not ITOP1 is preventing cancer from coming back. One of the most unique aspects of this study is the dosing regimen. Participants will receive a first (prime) dose four weeks after the first course of chemotherapy and before the surgery. A second (boost) dose is sequenced before the second course of chemotherapy.

This carefully balances two critical objectives. First, participants will still receive the best standard of care for oesophageal cancer. Second, dosing ITOP1 before surgery and a second round of chemo (in the neoadjuvant setting) is a very intentional departure from how previous cancer vaccines have been administered. The goal is to vaccinate far earlier in both disease and treatment progression while the immune system is healthy. If the primary tumor is also still present, there will be the potential for the immune system to recognize more cancer epitopes than what is included in the vaccine (called epitope spreading) to drive a more robust anti-cancer response.

VISTA will be one of the first studies in the world testing a cancer vaccine in the neoadjuvant setting. Professor Mark Middleton, who is VISTA’s Chief Investigator, the Head of Oncology at the University of Oxford, and Scientific Advisory Board Member for Infinitopes, said, 

“This first trial in oesophageal cancer will evaluate ITOP1’s precision targeting, which enables anti-tumour immunity through epitope spreading to tackle residual cancer cells and prevent recurrence. We are particularly excited that, by working with the MHRA, we can test ITOP1 where we believe it will achieve the best protection, in potentially curable disease.”

We are particularly excited by that, too.

Right Team

Synthesizing biological, computational, and clinical insights to arrive at the “the right antigen, the right delivery technology, and the right [clinical] setting” for a cancer vaccine is an enormous challenge. It requires an equally broad set of technical experts to come together to form the right team.

Infinitopes was designed and cofounded by Jonathan Kwok, the President & CMO of the business. After his medical training, Jonathan became a top-ranked (literally, #1) equity research analyst in biotech investment banking. After working with several massively successful biotechs on the IB side, Jonathan thought, “I think I can do this too!” So he jumped back into academic research as a graduate student at Oxford. There, he partnered with Lian Ni Lee and Senthil Chinnakannan, who were already working on a powerful viral system for stimulating T-cells.

After promising early results in cancer models, the three spun Infinitopes out of Oxford in 2021 and were off to the races. Since starting, Infinitopes has weathered one of the most challenging biotech markets in history while developing their platform and rapidly pushing into the clinic. This is no small feat.

As the company scaled, the leadership team has, too. Jo Brewer has joined Infinitopes as the CSO and interim COO. Formerly, Jo was the CSO of Adaptimmune, where she played a critical role in achieving the first FDA approval for a T cell therapy targeting a solid tumor. And Dan Menichella has joined the business as the CEO. Dan was the CEO and CBO of CureVac (acquired by BioNTech), where he led a $1.7B deal with Eli Lilly for cancer vaccine development. Infinitopes has a rare blend of brilliant first-time technical founders and leaders who have delivered FDA approvals and massive deals. This is a testament to their ambitious vision and impressive science, and exactly the kind of diversity of backgrounds that we seek out at Amplify.

We can’t think of a better team to take on the challenge of lining up all of the pieces needed to make precision cancer vaccines a reality. It’s a true privilege to partner with the Infinitopes team at such a pivotal moment.

If Infinitopes succeeds, the future of cancer care could look very different. As Jonathan says, our North Star is nothing short of “making cancer history.”