The trial was evaluating its live biotherapeutic, MRx0518, in combination with Bavencio (avelumab), a PD-L1 blocking antibody, as a first-line maintenance therapy for patients with unresectable locally advanced or metastatic urothelial carcinoma that had not progressed with first-line platinum-containing chemotherapy.
“We are continuing to build a strong body of evidence to support MRx0518 as a novel immunotherapy with broad potential to address significant unmet need across multiple oncology indications,” said 4D Pharma’s chief scientific officer, Dr Alex Stevenson.
“MRx0518 has previously demonstrated single agent immuno-modulation of the tumor microenvironment, and this data supports the potential of this combination to significantly enhance and improve outcomes for patients beyond treatment with Bavencio alone.”
Live Biotherapeutic products (LBPs) are defined by the FDA as biological products that contain a live organism, such as a bacterium, that is applicable to the prevention, treatment, or cure of a disease.
4D pharma, which has its HQ in Leeds in the UK, says its LBPs are orally delivered single strains of bacteria that are naturally found in the healthy human gut.
It has developed a proprietary platform, MicroRx, that rationally identifies LBPs based on a deep understanding of function and mechanism.
In March, the LPB developer announced positive interim results from the phase I/II study of the combination of MRx0518 and Keytruda (pembrolizumab), the anti-PD-1 therapy of MSD, for patients with solid tumors that have progressed on a prior immune checkpoint inhibitor (ICI). The renal cell carcinoma (RCC) group met its primary efficacy endpoint ahead of enrollment completion.
4D Pharma’s CEO, Duncan Peyton, told us then:
“The primary endpoint for Part B set by 4D Pharma and MSD was for more than three patients out of a total of up to 30 patients per tumor type group to achieve clinical benefit. Out of the first 16 evaluable RCC patients we have already hit four with clinical benefit, achieving the primary in this group. The RCC group and other tumor type groups will continue to enroll so we may see more than four, but we have already achieved that threshold.
“Clinical benefit is defined as complete response, partial response, or stable disease [equal to or greater than] 6 months.
"Including results from the completed Part A previously announced, out of 24 evaluable RCC patients we have achieved clinical benefit in eight. By another common metric - disease control rate - defined as complete response, partial response, or stable disease for at least nine weeks, we have, to date, seen 12/24 (50%).
“In this group of patients, who have had an average of three prior lines of therapy, including a previous immune checkpoint inhibitor, and are not responding to available therapies, this is a meaningful benefit – we now have patients on treatment for over two years.”
Asthma linked developments
4D Pharma also recently shared data from Part A of the Phase I/II trial of MRx-4DP0004 for the treatment of asthma at the 2022 American Thoracic Society (ATS) International Conference, in San Francisco.
That readout showed 83.3% of patients that received MRx-4DP0004 reported improved Asthma Control Questionnaire (ACQ) results, compared with 56.3% who received the placebo, and that the treatment continues to be safe and well tolerated, with no adverse events reported.
Commenting on that data on a call with us last week, Peyton said: “The metrics that you look at in terms of the ACQ scores include how the patient feels in terms of the control of their asthma, how often they have to take their inhaler, how well they sleep, how many times they get breathless. With the asthma study, what we were really impressed with, what we saw against placebo, was a significant reduction in people using their inhaler in those taking MRx-4DP0004.
"We are just about to commence the Part B study in 90 patients but we are enthused by what we have seen: MRx-4DP0004 is pretty much hitting all the endpoints that the Global Initiative for Asthma (GINA) is looking for – reduction in inhaler use, reduction in ACQ scores, reduction in exacerbations. We are really encouraged by that and looking forward to see how that data reads out in a bigger cohort of patients.”
The market that 4D Pharma can potentially address in terms of asthma treatment is quite broad, said Peyton. Part B of the trial will include patients with more severe symptoms. “Sites are being initiated now. We should have data published towards the end of 2023.”
Though, it is still taking longer to get clinical trial sites established due to ongoing COVID-19 restrictions, stressed the CEO.
Peyton, on that call, also acknowledged some of the challenges US microbiome-based companies have been experiencing in the past couple of months such as Finch Therapeutics, which in April announced it was forced to shed a percentage of its workforce, and Kaleido Biosciences, which revealed last month that it was winding up operations.
But the 4D Pharma lead stressed the fundamentally different approaches his company takes in terms of targeting the disease pathway compared to many microbiome focused firms.
“You have companies that are using consortia and are trying to change the environment of the gut to improve an outcome and companies like 4D Pharma at the other end of spectrum that are actually targeting very different mechanisms, like, for example, in Parkinson’s disease and in asthma, where we are targeting the immune system in terms of the outcomes that we want. The approaches are miles apart.”
He said consortia-based approaches can be effective in tackling diseases such as C. difficile infection. “But where you really need to hit the immune system, either to rev it up like we need to do in relation to oncology, and where we need to dampen it down, as in the case with asthma, that is an entirely different approach, where you need to have a more focused, mechanistic drug like [model of development], and that is where 4D Pharma sits."
Peyton also gave us his perspective on the current biotech fundraising landscape, with a lot of US biotech firms recently experiencing a cash crunch and investor sentiment in the sector looking like it is waning “The markets are really jittery at the moment, with inflationary pressures and interest rate concerns.”
XBI, an equal-weighted index tracking performance of US biotechnology stocks, is down around 65% in the last 12 months, said the 4D Pharma lead, as a way of illustrating that flight of capital from the sector.
“During the pandemic, the more generous funds were looking for places to put their capital, with all the excitement around COVID-19 vaccines, and mRNA, and suddenly biotech became hot and almost like a defense sector. A massive amount of money flowed into the sector in 2020, and up to early 2021. There was a huge number of companies funded.”
Now, he said, the biotech sector is starting to see a return to pre-pandemic levels of investment. He reckons the controversy over Biogen's Aduhelm and its challenged market roll-out, for one, hasn’t helped; it made investors nervous.
But Peyton said it is increasingly evident that there is a real need and desire to bring new therapies into that sector, both for Alzheimer's disease and Parkinson's disease. "Neuro degeneration is the next frontier. I think there is going to be an explosion of growth in that therapeutic class."