Biodexa Enters Agreements to Acquire Exclusive Worldwide License to a Phase 2 Ready Asset for Type 1 Diabetes

Biodexa Pharmaceuticals PLC recently announced it has entered into an agreement for the assignment of Adhera Therapeutics, Inc.’s rights to tolimidone (formerly coded MLR-1023) under an exclusive, worldwide, sub-licensable license from Melior Pharmaceuticals I, Inc. to develop, manufacture, commercialize, or otherwise exploit tolimidone.

Tolimidone was originally discovered by Pfizer Inc. and was developed through Phase 2 for the treatment of gastric ulcers. Pfizer undertook a broad preclinical program to characterize the pharmacology, pharmacokinetics, metabolism, and toxicology of tolimidone. Pfizer discontinued development of the drug due to lack of efficacy for that indication in a Phase 2 clinical trial. Tolimidone is a selective activator of the enzyme lyn kinase, which increases phosphorylation of insulin substrate -1, thereby amplifying the signaling cascade initiated by the binding of insulin to its receptor.

Stephen Stamp, CEO and CFO of Biodexa, said “Tolimidone offers the exciting potential to radically improve disease management for millions of Type-1 diabetes patients. We are eager to initiate a Phase 2 clinical program as expeditiously as possible to deliver a positive impact on those patient’s lives. For Biodexa, we believe this deal will significantly strengthen and diversify our pipeline offering existing and new investors greater opportunities for value creation.”

Biodexa plans to develop tolimidone for the treatment of Type-1 diabetes (T1D). Tolimidone’s potential utility in T1D has been demonstrated by several ground-breaking studies conducted by Professor Jean Buteau at the University of Alberta, where lyn kinase was identified as a key factor for beta cell survival and proliferation in in vitro and in vivo models. Most importantly, tolimidone was able to induce proliferation in beta cells isolated from human cadavers. From a mechanism of action perspective, tolimidone has been shown to both prevent beta cell degradation and to stimulate beta cell proliferation.

As a first step in the planned continued clinical development of tolimidone, the company intends to conduct a Phase 1b dose confirmation study in conjunction with the Alberta Diabetes Institute at the University of Alberta to establish the minimum effective dose of tolimidone in patients with T1D. The Phase 2 study is expected to be a double-blind, placebo-controlled study of approximately 35 patients with T1D over a period of four months with C-peptide levels as primary end-point. C-peptide is known to correlate with insulin levels in the body.

T1D and Type 2 diabetes (T2D) both occur when the body cannot produce sufficient levels of insulin, the hormone essential for regulating glucose levels in the blood. Insufficient levels of insulin results in high blood sugar levels  leading to potentially serious complications. T1D usually appears first in children and adolescents, but it can also occur in adults. In T1D, the body’s immune system attacks pancreatic beta cells so that they can no longer produce insulin. The causes of T1D are not fully understood and there is currently no cure. Patients with T1D are dependent on daily administration of insulin (via injection or infusion). In a meta analysis of 1,202 articles and 193 studies, the incidence of T1D was shown to be 15 per 100,000 with a prevalence of 9.5 per 10,000 of the population¹.

Melior initially evaluated tolimidone for the treatment of T2D. In studies conducted in in vivo models of T2D diabetes, tolimidone decreased blood glucose levels in mouse and rat oral glucose tolerance tests, in db/db mice and Zucker rats. Blood glucose lowering was produced with both acute and chronic dosing regimens.

Melior, in partnership with Bukwang Pharmaceutical Co. Ltd., conducted two Phase 2 studies in T2D. In the first Phase 2 study, 130 patients were treated with four active doses; 100 mg once daily, 100 mg twice daily, 200 mg once daily and 200 mg twice daily for 4 weeks. The primary endpoint was a mixed meal tolerance test, or MMTT, conducted on day 1 and day 29 and fasting plasma glucose, or FPG, was monitored weekly. Top line results from analyses of covariance, or ANCOVA, showed statistically significant (p=0.0079) improvement in MMTT and FPG in the 100-mg once daily dosed group. In addition, there was a statistically significant decrease in MMTT in the 100-mg twice daily dosed group. In general, favorable drug effects in all dose groups were suggestive of decreases in MMTT and FPG even when not statistically significant. Beneficial changes were also observed in all lipid parameters, though only triglycerides exhibited statistically significant differences.

In connection with the assignment, the company agreed to pay up an upfront payment to Adhera and certain secured noteholders of Adhera, in the form of cash, with respect to Adhera, and the company’s American Depositry Shares, with respect to the secured noteholders, and such parties are eligible to receive additional payments, in the form of cash and/or American Depositary Shares, upon the achievement of certain milestones. In addition, in connection with the license, the Company has agreed to issue to Melior and Bukwang American Depositary Shares. The Company would also be obligated to pay single digit tiered royalties on net sales of tolimidone.

The assignment of rights by Adhera, and the related effectiveness of the license, are each subject to certain closing conditions. The transaction is expected to close in the fourth quarter of 2023.

Biodexa Pharmaceuticals PLC is a clinical-stage biopharmaceutical company developing a pipeline of products aimed at primary and metastatic cancers of the brain.  The company’s lead candidate, MTX110, is being studied in aggressive rare/orphan brain cancer indications, including recurrent glioblastoma and diffuse midline glioma.

MTX110 is a liquid formulation of the histone deacetylase (HDAC) inhibitor, panobinostat. This proprietary formulation enables delivery of the product via convection-enhanced delivery (CED) at potentially therapeutic doses directly to the site of the tumor, by-passing the blood-brain barrier and avoiding systemic toxicity.

Biodexa is supported by three proprietary drug delivery technologies focused on improving the bio-delivery and bio-distribution of medicines.  Biodexa’s headquarters and R&D facility is in Cardiff, UK.  For more information, visit www.biodexapharma.com.