180 Life Sciences Corp. CEO James Woody, MD, PhD Issues Letter to Shareholders
PALO ALTO, Calif., Dec. 29, 2022 – 180 Life Sciences updates shareholders on clinical programs targeting Dupuytren’s disease, frozen shoulder, and postoperative delirium. A phase 2B trial on Dupuytren's showed promising results, with plans for a UK marketing authorization application targeted for mid-2023. The company is enhancing recruitment strategies for the frozen shoulder trial, while preparations for the postoperative delirium trial are on track. Despite ongoing litigation, the company believes it is in a stronger cash position following recent financing and a completed reverse stock split.
- Phase 2B trial for Dupuytren’s contracture exceeded expectations and showed potential cost-effectiveness.
- Plans to file for marketing authorization in the UK by mid-2023, indicating progress in regulatory pathway.
- Recent financing improved cash position, supporting clinical program advancement.
- Enrollment for the frozen shoulder trial is slower than anticipated in the UK due to patient access issues.
- MHRA noted that reducing nodule size does not guarantee improved disease progression outcomes.
PALO ALTO, Calif., Dec. 29, 2022 (GLOBE NEWSWIRE) --
Dear Fellow Shareholder,
As we come to the end of 2022, I am pleased to provide an update for our shareholders. In keeping with good corporate practice and US Securities and Exchange Commission (SEC) regulations, we have refrained from answering individual queries from shareholders until we were able to provide information to all shareholders at the same time.
Our priorities continue to be our clinical programs, repurposing anti-Tumor Necrosis Factor (TNF) drugs for treating Dupuytren’s disease, frozen shoulder and post-operative delirium.
The Dupuytren’s contracture trial phase 2B trial, led by Prof Nanchahal, the results of which we have previously announced, exceeded our expectations. It also showed that the treatment is likely to be cost-effective. Now, after obtaining scientific advice from the UK Medicines and Healthcare products Regulatory Agency (“MHRA”), the UK equivalent of the US Food and Drug Administration (“FDA”), and after discussions with our regulatory consultants in the United States and United Kingdom, we made the decision to begin preparing all the material necessary to seek marketing authorization in the UK. Based on the guidance received from our regulatory consultants on the time required to prepare the marketing authorization application, we currently plan on filing the application in mid-2023. In seeking a marketing authorization, we plan to engage a specialized consultant, Dr. Keith Watson, who spent nearly five years with the MHRA as a reviewer of biologics product applications, later serving as Director of Global Regulatory Affairs, Biologics Strategic Development Group at AbbVie, and more recently Vice President of Regulatory Affairs for Celltrion Inc. He now manages his own regulatory consulting practice. After reviewing our program and data, Dr. Watson stated, “This is re-purposing of an approved medicine for a new indication. Since Dupuytren’s contracture may be considered a seriously debilitating disease where there is an unmet medical need to be fulfilled, it may be possible to seek a Conditional Marketing Authorization (CMA) to include in our submission a real-world data (RWD) study comparing adalimumab to current standard of care in Dupuytren’s contracture with the objective of showing superiority.”
Dupuytren’s disease begins as a small nodule in the palm of the hand. Over time, the cells in this nodule generate fibrous cords, that pull the fingers into the palm. The team led by Professor Nanchahal discovered that injecting anti-TNF drugs into the nodule may have the potential to stop this process. All current therapies, of which surgery is the most common, can be used only when the fingers are contracted and the patient already has the disability. The participants recruited to the phase 2b clinical trial had nodules of early-stage Dupuytren’s disease, which were injected with anti-TNF or placebo. The trial met the primary endpoint of nodule hardness and the secondary endpoint of nodule size at 12 months. It is noteworthy that both the hardness and size of the nodules continued to decrease further for a period of 9 months after the final injection. Because it is a slowly progressing disease, participants would need to be followed for many years to show a significant difference in the development of finger contractures or progression to surgery, which is not practical given the very slow progression of the disease.
A published study from the Netherlands showed that increase in nodule size correlates with finger flexion deformity and we reason that a reduction in nodule size would conversely mean that fingers are less likely to contract. As previously disclosed, the MHRA reviewed the primary and secondary endpoints in the phase 2b trial and the data provided by the Company and noted that it has not been shown that reducing nodule size via treatment would lead to improvements in terms of Dupuytren’s disease progression. We plan to continue to collect all available data to address the point made by the MHRA. In addition, we may conduct a follow-on study to address the requirements of the MHRA, the EU, and the US FDA. We expect Dr. Watson will provide us advice regarding the best path forward assuming we receive Conditional Marketing Authorization (CMA). With the recent financing complete, the Company is proceeding with the preparation of the necessary CMA application documents. It is a very substantial, but worthwhile task.
When the Dupuytren’s trial was started, the only available high concentration, citrate free preparation of adalimumab was Humira from AbbVie. However, we are now aware of seven other companies with similar preparations and we are in contact with several of them with a view towards a potential future partnering arrangement.
Enrollment to the trial of anti-TNF for early-stage frozen shoulder is slower than anticipated in the UK as patients typically present to physical therapists and the processes are subject to delays. In the USA, all such patients are seen by orthopedic physicians, who are relatively easy to access. The trial team has implemented several strategies to improve recruitment and we hope that these will be effective.
Preparation for the trial of anti-TNF to prevent the development of postoperative delirium remains on track and we anticipate that the first patient will be recruited in the first half of 2023.
Our focus remains on our clinical portfolio which is the three new indications for TNF blockade discussed above and we plan to continue to evaluate the timing and cost/benefit of additional ongoing research for our early discovery programs.
Our HMGB1 program continues to advance slowly. The molecular dynamics for the binding of this molecule are extremely complex and potentially need more extensive research in order to identify a lead candidate.
The synthetic cannabinoid program is also moving along, albeit slower than expected, with an emphasis on more effective formulations to ensure that the cannabinoids are much more orally available, as they are currently very poorly absorbed. We are continuing with our research in this field towards the development of a treatment for chronic pain. Assuming that the oral formulation research efforts are successful, we may initiate early trials in patients suffering from chronic pain, perhaps in early 2024.
As most of you know, we remain in some ongoing litigation and at this point we have no further update on such matters other than what has been reported in extensive detail in our most recent Quarterly Report on Form 10-Q.
With the recent 1-for-20 reverse stock split being completed in December, the Company expects to be in compliance with Nasdaq’s ongoing listing rules. With a reduced burn rate and the financing we have just completed, the Company is in a stronger cash position to move forward with the programs outlined above, with the caution that drug development and the process of dealing with regulatory agencies is a slow and methodical process that may move slower and be more difficult than we and our shareholders would desire. However, we remain confident that we will be able to move our products ahead as we have described.
Sincerely,
James Woody MD, PhD
CEO, 180 Life Sciences
About 180 Life Sciences Corp.
180 Life Sciences Corp. is a clinical-stage biotechnology company focused on the development of novel drugs that fulfill unmet needs in inflammatory diseases, fibrosis and pain by leveraging the combined expertise of luminaries in therapeutics from Oxford University, the Hebrew University and Stanford University. 180 Life Sciences is leading the research into solving one of the world’s biggest drivers of disease – inflammation. The Company is driving groundbreaking studies into clinical programs, which are seeking to develop novel drugs addressing separate areas of inflammation for which there are no effective therapies. The Company’s primary platform is a novel program to treat fibrosis using anti-TNF (tumor necrosis factor).
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the accuracy of simulations and the ability to reproduce the outcome of such simulations in real world trials; 180 Life Sciences’ reliance on third parties to conduct its clinical trials, enroll patients, and manufacture its preclinical and clinical drug supplies; the ability to come to mutually agreeable terms with such third parties and partners, and the terms of such agreements; estimates of patient populations for 180 Life Sciences planned products; unexpected adverse side effects or inadequate therapeutic efficacy of drug candidates that could limit approval and/or commercialization, or that could result in recalls or product liability claims; 180 Life Sciences’ ability to fully comply with numerous federal, state and local laws and regulatory requirements, as well as rules and regulations outside the United States, that apply to its product development activities; the timing of filing, the timing of governmental review, and outcome of, planned Investigational New Drug (IND) applications for drug candidates; 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These risk factors and others are included from time to time in documents the Company files with the Securities and Exchange Commission, including, but not limited to, its Form 10-Ks, Form 10-Qs and Form 8-Ks, and including the Annual Report on Form 10-K for the year ended December 31, 2021, and Quarterly Report on Form 10-Q for the quarter ended September 30, 2022, and future SEC filings. These reports and filings are available at www.sec.gov and are available for download, free of charge, soon after such reports are filed with or furnished to the SEC, on the “Investors”—“SEC Filings”—“All SEC Filings” page of our website at www.180lifesciences.com. All subsequent written and oral forward-looking statements concerning the Company, the results of the Company’s clinical trial results and studies or other matters and attributable to the Company or any person acting on its behalf are expressly qualified in their entirety by the cautionary statements above. 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FAQ
What were the results of the Dupuytren’s contracture trial for ATNF?
When does 180 Life Sciences plan to file for marketing authorization in the UK for ATNF?
What challenges is 180 Life Sciences facing with the frozen shoulder trial for ATNF?
How is the company addressing concerns raised by MHRA regarding Dupuytren’s disease treatment?
