On September 30, 2021 4D pharma plc (AIM: DDDD), a pharmaceutical company leading the development of Live Biotherapeutics, reported the interim results for the Company and its subsidiaries (together "the Group") for the six months ended 30 June 2021 (Press release, 4d Pharma, SEP 30, 2021, View Source [SID1234590515]).
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All details stated hereafter relate to the UK IFRS accounts; the Group also produces US GAAP accounts, the details of which are included in the Form 6-K to be filed with the U.S. Securities and Exchange Commission.
Financial highlights
●Net assets at 30 June 2021 of £39.7 million (30 June 2020: £31.5 million and 31 December 2020: £28.0 million).
●Cash and cash equivalents and short-term deposits at 30 June 2021 of £20.7 million (30 June 2020: £10.0 million and 31 December 2020: £8.8 million).
●Loss and total comprehensive income for the six months ended 30 June 2021 of £56.1 million (30 June 2020: £13.6 million and 31 December 2020: £25.9 million).
●Research and development expenditure for the six months ended 30 June 2021 of £9.9 million (30 June 2020: £12.4 million and 31 December 2020: £22.0 million).
Operational highlights
●Completed the acquisition of Longevity Acquisition Corporation (Longevity), a special purpose acquisition company (SPAC), and the listing on NASDAQ of 4D pharma American Depository Shares (ADSs) under the ticker symbol ‘LBPS’. As a result of the business combination, cash of $14.8 million held by Longevity became available to 4D pharma.
●In conjunction with the merger and NASDAQ listing, 4D pharma completed a private placement raising gross proceeds of approximately $25.0 million (£18.0 million), including participation of existing investor Merck Sharp & Dohme Corp.
●Presented additional supportive data from the completed Phase II trial of Blautix in subjects with irritable bowel syndrome with constipation (IBS-C) or with diarrhea (IBS-D) at Digestive Disease Week (DDW). The DDW 2021 poster can be accessed via the Posters & Publications page of our website at View Source." target="_blank" title="View Source." rel="nofollow">View Source
●Announced the completion of target enrollment of 30 patients in Part A of the Phase I/II first-in-human clinical trial of MRx-4DP0004 for the treatment of asthma.
●Announced a clinical trial collaboration and drug supply agreement with Merck KGaA, Darmstadt, Germany, and Pfizer Inc. for BAVENCIO (avelumab). Under the collaboration, 4D pharma intends to commence a clinical trial to evaluate BAVENCIO in combination with MRx0518 as a first-line maintenance therapy for patients with locally advanced or metastatic urothelial carcinoma that has not progressed with first-line platinum-containing chemotherapy. This is the second clinical collaboration combining MRx0518 with an immune checkpoint inhibitor.
●Also provided a clinical update on the MRx0518 clinical program, with updates on patient recruitment and study status across the three ongoing MRx0518 clinical trials.
●Entered into a collaboration with Parkinson’s UK, a non-profit organization, to establish a Patient Advisory Board to present patient-centric perspectives as the Company advances novel Live Biotherapeutics for the treatment of neurodegenerative conditions such as Parkinson’s disease.
●Announced the appointment of John Beck as Chief Financial Officer.
●Announced the appointment of Paul Maier as Non-Executive Director.
Since the period end
●Announced the passing of John Beck, Chief Financial Officer.
●Published pre-clinical research relating to its second-generation immuno-oncology LBP MRx1299 improving the activity of CAR-T.
●Announced the acceptance of two e-Poster presentations of MRx0518 clinical biomarker data at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress, held from 16–21 September 2021. The ESMO (Free ESMO Whitepaper) 2021 posters can be accessed via the Posters & Publications page of our website at View Source." target="_blank" title="View Source." rel="nofollow">View Source
●Closed a senior secured credit facility for up to $30 million with Oxford Finance SARL, in three tranches: an initial tranche of $12.5 million at closing which extends 4D pharma’s cash runway into Q4 2022, with the remaining $7.5 million and $10 million tranches dependent on the achievement of certain milestones.
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As we move into the second half of 2021, we look forward to capitalizing on the efforts of the team throughout the first six months of 2021. We have generated more data expanding our unique understanding of mechanisms of host-microbe interactions and are seeing the benefits in our clinical programs while we continue to drive research through our proprietary MicroRx platform. This work has allowed us to discover new therapeutic possibilities in disease such as Parkinson’s, and demonstrate potential of our Live Biotherapeutics alongside new modalities such as CAR-T. Alongside the continued push to bring our Live Biotherapeutics to an approval in oncology, 4D pharma achieved a significant milestone at the beginning of the year following our listing on NASDAQ.
Building the oncology franchise
We continue our commitment to oncology, building a strong understanding of the utility of our Live Biotherapeutics in this field. In particular recognizing the value of a therapeutic which has little or no side effects to combination with existing therapies in the fight against cancer while many other combination treatments currently evaluated in immune-oncology increase toxicity.
With our lead oncology candidate MRx0518, we have built on our ongoing work with MSD (Merck & Co.) and its anti-PD-1 immune checkpoint inhibitor (ICI) Keytruda (pembrolizumab), announcing a new clinical collaboration and drug supply agreement with Merck KGaA and Pfizer and their anti-PD-L1 ICI Bavencio (avelumab). In contrast to the ongoing study with Keytruda in ICI-refractory patients, the new Bavencio collaboration takes MRx0518 into earlier lines of treatment, and expands our clinical portfolio targeting the PD-1 axis.
Under the collaboration we will conduct a clinical study to evaluate MRx0518 in combination with Bavencio as a first-line maintenance therapy for urothelial carcinoma, a common form of bladder cancer. Bavencio is the first and only ICI approved in this setting, and we are excited to commence this fourth clinical study of MRx0518 before the end of 2021.
In addition, we announced progress updates for the three ongoing clinical studies of MRx0518 – in combination with Keytruda in patients with solid tumors refractory to prior ICI therapy; as a neoadjuvant monotherapy; and in combination with radiation prior to surgery for pancreatic cancer. These studies continue to progress well, giving more insights into the biological mechanisms of MRx0518 and its activity on the patient immune system, potentially allowing us to understand which patients may benefit most from MRx0518 in combination with ICIs like Keytruda and Bavencio.
After the period end, in September, 4D pharma presented new data from the Keytruda combination and neoadjuvant monotherapy studies at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress. The ESMO (Free ESMO Whitepaper) 2021 posters can be accessed via the Posters & Publications page of our website at View Source." target="_blank" title="View Source." rel="nofollow">View Source The new data includes tumor immune biomarkers associated with response to the combination with MRx0518 and Keytruda, which is an exciting proposition we look forward to investigating further as we continue to progress MRx0518. This is supported by additional data for MRx0518 as a monotherapy, providing further evidence of immune activation by our oral Live Biotherapeutic, including positive changes in prognostic indicators predictive of response to immunotherapy. These data continue to deepen our understanding of the activity of MRx0518 on patients, and will help inform engagement with regulatory authorities and clinicians as we continue to develop this leading immuno-oncology Live Biotherapeutic.
The main focus of our work in oncology at this time is the preparation of a pivotal development program for MRx0518 in an oncologic indication.
Through our clinical programs and research, our work in oncology illustrates the potential of the MicroRx platform to expand 4D pharma’s leadership in oncology.
Alongside our work in solid tumors, 4D also continues to push forward in identifying new LBP candidates in additional oncology settings, such as CAR-T. 4D pharma recently published pre-clinical research relating to second-generation oncology LBP MRx1299 in the respected peer-reviewed journal Nature Communications. The research demonstrates the ability of the bacterium Megasphaera massiliensis and its short chain fatty acid (SCFA) metabolite pentanoate to enhance the anti-tumor activity of cytotoxic T lymphocytes (CTL) and Chimeric antigen receptor T cell (CAR-T) therapies in animal models of cancer.
Blautix – a leading late-stage LBP candidate
IBS remains a misunderstood disease and not easily characterized. In the US, as many as 35 million people report IBS symptoms, with 60-70% being women. IBS remains a disease with significant unmet need. Current treatments target sub-type specific symptoms (diarrhea or constipation) but, due to side effects and sub-optimal efficacy, patient satisfaction and compliance remains an issue. Further, there currently is no therapeutics approved for patients with fluctuating or mixed symptoms, known as IBS-M.
Following publication of topline efficacy and safety results from our Phase II study of Blautix in irritable bowel syndrome with constipation (IBS-C) and with diarrhea (IBS-D) in October 2020, important additional data was presented at Digestive Disease Week (DDW) in May 2021. The DDW 2021 posters can be accessed via the Posters & Publications page of our website at View Source . A key finding from sub-group analyses was an unusually high placebo response rate in patients in the UK and Ireland which negatively impacted the topline results. Conversely, we saw an enhanced effect in the US population in both IBS-C and IBS-D.
In agreement with regulatory guidelines and key opinion leader feedback, the positive Phase II data provides a clear path forward for the development of Blautix as a novel treatment for IBS with the potential to be a single, safe, effective therapeutic able to address multiple subtypes of IBS. We have engaged with the US FDA regarding plans for pivotal development, and discussions are ongoing with multiple potential partners for the program.
MRx-4DP0004 – Systemic immune activity via the gut
MRx-4DP0004 is in an ongoing Phase I/II first-in-human clinical trial in patients with partly controlled asthma, as an add-on therapy to their long-term maintenance asthma medication.
In June we announced the completion of target enrolment of 30 patients in Part A of our Phase I/II randomized, placebo-controlled study of asthma candidate MRx-4DP0004. Part A of the trial primarily assesses the safety and tolerability of MRx-4DP0004, as well as biomarker signals of activity relevant to asthma. We expect to announce top line results later in 2021.
Leveraging the gut-brain axis
As accumulating evidence points towards the gut-brain axis and the role of the microbiome in conditions of the central nervous system (CNS), we are excited to continue to push forward in this field. In April, the company announced our collaboration with Parkinson’s UK, to establish a Patient Advisory Board (PAB) of people living with Parkinson’s disease. The PAB provides valuable patient perspectives as we continue to advance candidates MRx0029 and MRx0005 towards a first-in-man study in patients with Parkinson’s disease expected to begin in 2022.
Corporate activity
The NASDAQ is the premier exchange for biotechnology companies worldwide, giving companies global reach and visibility within the healthcare investment ecosystem. Achieving a listing on NASDAQ has been a strategic objective for 4D pharma’s continued growth and success moving forward.
In March 2021 we met this transformational milestone, as we listed 4D pharma American Depository Shares (ADSs) on the NASDAQ exchange in the United States following the completion of our merger with special purpose acquisition company (SPAC) Longevity Acquisition Corporation.
In conjunction with the SPAC merger and NASDAQ listing we conducted a fundraise which together provided the company with approximately $42 million of additional capital. In doing so we began to strengthen our international investor base and put 4D pharma in a strong financial position to execute across our pipeline.
Further, after the period end in July, we also announced a credit facility with Oxford Finance LLC, that provides 4D pharma with up to $30 million of capital across three tranches, of which the first tranche of $12.5 million was received upon closing. The facility diversifies and strengthens the company’s capital structure with a well-respected specialty finance firm in the life sciences field. The additional funds further extend our cash runway beyond additional potentially transformative development milestones.
In addition to strengthening our financial position, we also strengthened our leadership team. In March we welcomed Paul Maier as a Non-Executive Director who will also serve as a financial expert under SEC and NASDAQ rules. Paul brings over 25 years of operational and financial management experience in the life sciences industry, and his experience has been a valuable addition to our Board of Directors.
It was with great sadness that we announced the passing of John Beck in July of this year, who had served as Chief Financial Officer with the company since March. John was greatly respected within the life sciences industry and brought 30 years of finance experience to our team. His significant contributions to the company during his time with us have been highly valuable, and we hope to carry his legacy forward by building upon the strong foundations he helped to lay as 4D pharma entered a new era as a US-listed entity.
Conclusion
The first half of 2021 has been a significant period for 4D pharma. Our dual listing on NASDAQ raised our international profile and, using this as a platform along with new funds at our disposal, we look ahead to a period rich in clinical catalysts across our pipeline of Live Biotherapeutic Products taking the microbiome beyond the gut, including clinical readouts and the commencement of new studies across multiple programs. Highs and lows in the broader microbiome space have created mixed feelings towards microbiome therapeutic approaches – we are confident 4D pharma’s differentiated, mechanism-driven approach is poised to deliver.