PALO ALTO, Calif., Sept. 26, 2022 (GLOBE NEWSWIRE) — 180 Life Sciences Corp. (NASDAQ:ATNF) (“180 Life Sciences” or the “Company”), a clinical-stage biotechnology company today released the following letter to stockholders from its Chief Executive Officer, Dr. James Woody.
Dear Fellow Stockholder,
In mid-June, I wrote to update you on the status of our Company and our respective investments.
In that letter, I provided an update regarding the Company’s clinical development plans, which remained on track then, and continue to remain on track today. As a reminder, 180 Life Sciences was founded on the belief that novel anti-inflammatory biologics that are already approved, such as anti-tumor necrosis factor (TNF), or adalimumab, could have the potential to address large unmet needs for a variety of additional indications. Currently, we have an active clinical development program that includes Phase 2a and Phase 2b proof-of-concept data which we believe demonstrates that anti-TNF therapy can prevent the progression of Dupuytren’s disease in its early stages, as well as plans for two additional Phase 2 studies, one in frozen shoulder which has recently commenced, and the other in post-operative cognitive delirium (POCD), for which we just received grant funding. The POCD grant will allow 180LS to determine if administration of an anti TNF antibody, just prior to surgery, either reduces or eliminates the cognitive delirium often seen following surgery. This will be a randomized controlled clinical trial using Remsima, an anti TNF antibody supplied by Celltrion. We think all three indications share a similar underlying mechanism of being critically dependent on TNF. (1-3).
Fibrosis of the hand, known as Dupuytren’s disease, is a common chronic, progressive condition that causes the fingers to curl irreversibly into the palm and can be very disabling. In the early stage of the disease, TNF and other pro-inflammatory cytokines, recruit myofibroblasts that lead to fibrosis and the formation of a tiny lump, or nodule, in the palm of the hand. The nodule is the site where the cells which drive the disease reside. Approximately 20-35% of patients with a palmar nodule progress to finger contractures. (4). Patients with comorbidities, such as smoking and diabetes, are more likely to experience disease progression. Roughly 12 million patients in the U.S., 2.5 million in the U.K. and 22 million in the EU have Dupuytren’s disease.(5). Currently, there is no approved treatment for early-stage disease and patients must wait until the disease progresses with loss of hand function before undergoing surgery or treatment with collagenase. More than 50% of patients will experience a recurrence of Dupuytren’s disease within five years of non surgical intervention (6) and about 6 % after surgery (7). As such, there is a very large unmet need for patients with early-stage Dupuytren’s disease.
In April, we announced that positive Phase 2b data from our trial in Dupuytren’s disease had been published in The Lancet Rheumatology. As discussed in that publication, through extensive research of published medical literature, as well as direct clinical and drug development experience, Dr. Nanchahal, Chairman of the 180LS Clinical Advisory Board , believes that the treatment for Dupuytren’s disease is most effective during the early nodular stage of the disease, to prevent the development of cords and progression to finger contractures. Dr. Nanchahal’s investigation of anti-TNF therapy in Dupuytren’s disease in a small Phase 2a study(8) found, that intranodular injection of 40 milligrams (mg) of adalimumab in 0.4 milliliter (ml) resulted in down-regulation of the myofibroblasts that are responsible for fibrosis and the formation of the nodule in the early stage of Dupuytren’s disease.
Based upon the Phase 2a findings, he determined that a rigorous randomized, double-blind, placebo-control Phase 2b was warranted in order to attempt to further demonstrate that repurposing anti-TNF therapy for Dupuytren’s disease could be an effective treatment for early-stage disease and prevent progression. Based upon published medical literature, clinical experience and the findings from our Phase 2a study, we believed that a primary endpoint of nodule hardness and a secondary endpoint of nodule size could be effective indicators, or surrogates, of long-term disease progression in the absence of a clinical trial with a 10-year follow-up. The trial met its primary endpoint of nodule hardness and, importantly, also the secondary endpoint of nodule size. These were specified before the clinical trial was performed. The results were statistically significant when compared to placebo. Further there is published information indicating that module size correlates with eventual finger contraction (9). The significant and persistent reduction in nodule size as seen in the 2B trial (1) would be expected to delay or eliminate the progression to finger contraction.
This brings us to where we are today. We have a scheduled meeting during Q4 2022 with the U.K.’s Medicines and Healthcare products Regulatory Agency (MHRA) regarding our Phase 2b data in Dupuytren’s disease, based on the initial determination by MHRA that our chosen endpoints need further validation. At this meeting, we plan to submit evidence to the MHRA that supports our chosen endpoints. Once this data is submitted, we expect further discussions with the MHRA, in which they are expected to provide final guidance regarding the regulatory approval pathway of an anti-TNF therapy in early-stage Dupuytren’s disease. Knowing that this could take several months, we expect to gain clarity from the MHRA by late first quarter of 2023.
We also continue to remain in discussions with potential partners, and/or licensees for our Dupuytren’s program.
In terms of additional progress, we recently disclosed that the first patient in the preventative frozen shoulder trial, also funded by a National Institute for Health and Care Research (NIHR) grant, had received an injection in the trial. There are five active sites, and we will be observing how quickly patients can be enrolled in this trial to gain information on the potential use of anti-TNF agents to reduce or eliminate the need for surgical intervention in this debilitating disease. For the POCD trial, we are gathering all the regulatory approvals necessary to initiate patient treatment, anticipated by Q1 2023, or earlier.
In terms of the further development of intellectual property, we continue to make novel discoveries and file new patents. Most recently we discovered another pro fibrotic mechanistic pathway and showed that by blocking the protein interleukin-33 (IL-33) and TNF receptor 2 (TNF R2), the expression of the pro-fibrotic genes in myofibroblasts could be inhibited. The patent was issued earlier this year.
In closing, we continue to work diligently and efficiently to deliver treatment options for one of the largest drivers of disease, inflammation. Our active clinical development program currently consists of three potential indications and our clinical development plans for all ongoing programs remain on track. We believe that the successful execution of our current clinical development plans over the long-term could enhance stockholder value.
Sincerely,
/s/ James Woody MD, PhD
CEO, 180 Life Sciences
