Biofidelity’s ASPYRE: The future is bright for oncology


Genomic technology company Biofidelity has announced the launch of ASPYRE-Lung reagents (RUO) for research use, marking its second product launch this year, with the aim of providing simpler, faster analysis of comprehensive genomic biomarkers to existing solutions.

It follows the earlier and inaugural launch of the ASPYRE-Lung Laboratory Developed Test (LDT) back in September, at which juncture pharmaphorum spoke with Biofidelity’s co-founder and CEO, Dr Barnaby Balmforth, in order to discover more about the inroads the company is making towards decentralising genomic testing and enabling enhanced access to critical biomarker testing. The ASPYRE lung is a novel assay that simplifies and accelerates the detection of biomarkers for non-small cell lung cancer (NSCLC).

Working towards precision medicine in oncology

Founded in 2019, Biofidelity has two sites, with its R&D and product development based in Cambridge, UK, while its clear certified diagnostic laboratory is in the RTP area of North Carolina, USA, and is the location of the first product launch. Biofidelity’s medical affairs and commercial teams are also based out of the US.

“Everyone is aware that precision medicine is fantastic news for patients,” said Balmforth. “You now have this situation in which we can select the treatments that will best work for a specific patient. If that happens, the outcomes are far better. In some cases, non-small cell lung cancer is really the poster child for precision medicine.”

There are currently more than 25 FDA-approved therapeutics for treatment of NSCLC, which specifically target mutations in the patient's tumour. 

“If you are lucky enough to have one of these mutations and find it quickly and get onto the right treatment, the outcomes are far better for you,” Balmforth explained. “It can be as much as five- to tenfold better progression free survival.”

“As we were talking to physicians, it became apparent that we now have, I think for the first time, this weird scenario where therapeutics are outpacing diagnostics,” he continued. “You have those 25-plus different FDA-approved therapies, but they can only be deployed for patients who receive biomarker testing. That seems obvious. It's been in the guidelines for years now that these patients should all receive a multigene testing to determine which treatment will work for them. Despite that being the case, in the US, 65% of lung cancer patients start treatment without the recommended test results. If you look globally, that figure is about 80%, which means that you have $100 billion invested in developing these therapies, and they're only benefitting a tiny fraction of the patients for whom they could bring these enormous benefits.”

“It's bad news for pharma, it's bad news for patients,” he said. 

Poor access to biomarker testing: A problem to be solved

Despite some brilliant innovations within life sciences, sometimes what matters most – the patient – gets left behind.

“You go to ASCO and there's a lot of discussion about poor access to biomarker testing,” noted Balmforth. “To some extent, the industry moved on a little bit and I think it thought that treatment selection was now a solved problem and that we should all move on. There's been a lot of excitement about early detection and minimal residual disease and these new applications of genomics, but the reality is that patients are being left behind. That's really where we come in.”

“The goal for us has been to try and solve that problem, a problem that we see as being driven by complexity and centralisation of testing,” he said. “Next-generation sequencing is amazing as a technology, [but] it was never really designed for clinical use. In many clinical applications it can fulfil needs, and it's doing a reasonable job here, but the reality is that it is really expensive for laboratories to set up.”

Indeed, it requires batching of samples, which results in long turn-around times and high failure rates. 

“Hidden beneath the surface here is a situation where, for lung cancer patients, it typically takes three to five weeks to get sequencing results [and], typically, about 25% of samples that are sent for sequencing never generate a result,” explained Balmforth. “That is having a massive impact on these patients. That's where the technology we've developed is specifically targeted.” 

Biofidelity’s ASPYRE technology: Accelerating and cost saving

Just-launched APSYRE-Lung RUO runs on existing PCR instruments already available in laboratories and provides high sensitivity, enabling testing from tissue samples with as little as 10% tumour content, compared to 20% or 30% for most competing assays.

“The ASPYRE technology is essentially a method for performing high sensitivity, multigene testing on PCR instruments, which means that we can take a box of our reagents and ship them to a lab that has a PCR instrument and enable this testing to be run locally and much more quickly,” Balmforth said. “[It turns] around results the next day instead of three to five weeks later. The goal here is to try and bring the benefits of precision medicine to a far broader patient population.”

“What we are testing is everything that is in the treatment guidelines for non-small cell lung cancer and nothing else - we are very focused on delivering actionable information as quickly as possible,” he continued. “Ultimately, the goal for us is to enable global decentralisation of genomic biomarker testing. The way we achieve that is by launching reagent products that allow our customers to deploy our technology on their existing PCR instruments. Particularly in the post-COVID world, you have large networks of laboratories globally that were set up for COVID testing that are sitting there with PCR instruments and now looking for content to run on those platforms. Pretty much every healthcare system in the world has this challenge of, ‘How do you deliver on the promise of precision medicine for your patients without facing enormous costs of testing?’”

And that is where Biofidelity comes in: to address the challenges of PCR. 

“The two limitations of PCR are multiplexing, so PCR tests are limited to wrap typically one gene at a time, and in many healthcare systems they are still being used,” explained Balmforth. “You do a kind of serial set of PCR tests. You do one and, if there's a negative result, you do the next one, and then you do the next one, and then you run out of sample. Solving that multiplexing challenge is really important. Then, PCR also has limited sensitivity against that background of healthy DNA, which means where we've seen an increasing move into liquid biopsy – so, blood-based testing – [but] PCR has been unable to meet the sensitivity requirements. Those are the two things that our technology solves.”

An exciting future, including for clinical trials

Biofidelity will be launching reagents initially as a research product and taking those reagents through regulatory approval.

“We are very excited for the future in terms of the broad impact that we can have,” enthused Balmforth. “I would also highlight there's an intermediate step here, which is clinical trials. One of the challenges now, again, particularly in lung cancer, but also increasingly in other indications, is clinical trial enrolment. You have, for example, new therapies, which are targeting specific mutations, and require you to identify the patients who have those mutations, to get them on the trial, and that can be very expensive, and because of the turnaround times of centralised testing, you often lose patients.”

“Patients sign up for the trial, they get the test, but then their oncologist puts them on chemotherapy before the test results come back,” he continued. “Then, the other challenge is even therapeutics that are not targeting a specific mutation. [With] immunotherapies that are under trial, there is a requirement to screen patients before enrolment, to make sure they do not have a mutation. In lung, typically, you only need to screen three genes. No one wants to use a $5,000, 500-gene sequencing panel.”

“The lung cancer treatment guidelines only recommend screening of 11 genes,” Balmforth expanded. “Again, one of the reasons why sequencing tests are so vast in terms of number of genes is they're designed to cover every cancer, and there is one test you run on every patient regardless of which cancer they have. While that's efficient for the lab, it's not great for the payers in the healthcare systems who are paying for these very large tests. It's like, if you were suspected of having COVID, would you want a test that tested you for every possible infectious disease? You'd want a targeted test that tells you whether you have COVID or not, and this is the equivalent.”

“It takes three to five weeks to screen three genes to enrol someone on a clinical trial, and that is a massive challenge that, again, we are solving,” he stated. 

A golden age for cancer care

In the near future, Biofidelity hopes to deploy its reagents into CROs and clinical trial enrolment sites to make trial enrolment much more efficient.

“It is a golden age for cancer care,” said Balmforth. “We have this revolution in oncology in this dawning of precision medicine, and yet, until this point, a lot of patients in a lot of healthcare systems have simply not felt those benefits. There is a really acute need here to improve access to biomarker testing, and what's needed are new solutions that make things simpler, make things more affordable for healthcare systems, and deliver physicians what they're actually asking for.”

“I think the future is bright in oncology,” he reiterated. “I think we've made enormous strides forward, but I think we need to catch up on the diagnostic side. What Biofidelity has found is essentially a completely new technology, a method. The underlying technology on which we base our products is completely unique to us and has this unique set of properties, in that it solves the multiplexing challenge and sensitivity challenge of PCR, while retaining its simplicity and low cost and ease of adoption.”