Varlitinib Ditosylate

Biodexa Pharmaceuticals PLC (NASDAQ: BDRX) (“Biodexa” or the “Company”), a clinical stage biopharmaceutical company developing a pipeline of products aimed at primary and metastatic cancers of the brain is pleased to announce that it has signed non-binding letter of intent to potentially acquire Varian Biopharmaceuticals, Inc. (“VarianBio”), a private US precision oncology company developing novel therapeutics for the treatment of cancer. Background to the proposed acquisition In recent communications, the Company has referenced a shift in strategy from a drug delivery company to a therapeutics company. Currently, the Company’s only clinical asset is MTX110 which is being developed for three intractable rare and orphan brain cancers. The Company’s intention is to add to, and diversify, its development pipeline with a continued focus on rare and orphan products and/or oncology therapeutics and VarianBio represents the first of such opportunity. Information on VarianBio VarianBio is developing a high-potency, specific atypical protein kinase C iota (“aPKCi”) inhibitor with best-in-class potential as a treatment for various oncology indications with an initial focus on basal cell carcinoma (BCC) and molecularly targeted solid tumors. VarianBio’s rationally designed aPKCi small molecule inhibitor candidate that has been optimized for potency, selectivity and tolerability. aPKCi has been implicated as an oncogene in a number of human cancers, including BCC, cutaneous T-cell lymphoma (CTCL), non-small cell lung cancer (NSCLC), acute myeloid leukemia (AML), colorectal cancer, and pancreatic cancer, among others. aPKCi has also been demonstrated to have a role in allowing the immune system to recognize tumors, recruit immune cells into the area, and ramp up the anti-tumor response to kill cancer cells in the lab by shrinking their tumors. The active pharmaceutical ingredient in VAR-101/102, a novel aPKCi inhibitor, has demonstrated dose dependent anti-tumor activity in murine and human BCC cell lines, as well as other cancer models. VAR-101 will be developed in a topical formulation for BCC which has the potential to offer optimal clinical utility as a surgical neoadjuvant or adjuvant therapy. Following completion of IND-enabling skin toxicology studies, VAR-101 is targeting to start a Phase I proof-of-concept study in the first quarter of 2024. VAR-102, an oral formulation of the active aPKCi inhibitor, lends itself to broader applications in multiple tumor types. The Company believes that VAR-101 and VAR-102, if approved, could represent significant medical and commercial opportunities. Terms of the proposed acquisition Under the non-binding letter of intent, VarianBio will merge into an acquisition subsidiary of the Company and it is proposed that VarianBio equity and debt holders (together,“VarianBio Securityholders”) will receive 10MM of the Company’s American Depositary Shares (“ADSs”), at close as initial consideration. On a pro forma basis, prior to the planned financing discussed below, VarianBio Securityholders will own approximately 34% of the post-acquisition Company. VarianBio Securityholders will receive up to a further 6MM ADSs, issuable in two phases: 3MM upon the commencement of the first pivotal registration study of a VarianBio product and an additional 3MM upon the first FDA approval of a VarianBio product. In addition, pursuant to the non-binding heads of terms, the Company plans to raise not less than US$7.0MM, net of expenses, which will be used to fund VAR-101 through its Phase I proof-of-concept study that VAR-101 is targeting to commence in the first quarter of 2024. The acquisition agreement is also expected to contain other customary conditions, including shareholder approval, and appropriate representations and warranties by the parties.

Pass and Fail list with a pen. baona/Getty Images/iStockphoto The drug failed to meet the primary endpoints of progression-free survival and overall response rate. Singapore-based ASLAN Pharmaceuticals announced topline data from its TreeTopp (TREatmEnT OPPortunity with varlitinib in biliary tract cancer) trial in second-line biliary tract cancer (BTC). The drug failed to meet the primary endpoints of progression-free survival (PFS) and overall response rate (ORR). Varlitinib is an oral, reversible, small molecule pan-HER inhibitor that targets the human epidermal growth factor receptors, HER1, HER2 and HER4. These receptors are mutated or overexpressed in numerous cancer types, resulting in excessive proliferation and uncontrolled growth. The drug has been granted orphan drug designation by the U.S. Food and Drug Administration (FDA) for gastric cancer and cholangiocarcinoma, a sub-type of biliary tract cancer. It also received orphan drug designation for biliary tract cancer by South Korea’s Ministry of Food and Drug Safety. The trial was a global, double-blind, randomized two-arm study that enrolled 127 patients who failed first-line therapy. There were 56 sites in the U.S., Europe, Japan, Australia and other parts of Asia. In the trial, the median PFS was 2.83 months for varlitinib in combination with capecitabine compared to a median PFS of 2.79 in the control arm. In the varlitinib arm, ORR was 9.3% compared to 4.8% in the control arm. hbspt.cta.load(4413123, '92ebc33d-a4a8-4c10-b41e-a52c39dc69ea', {}); The trial didn’t hit statistical significance, but Aslan notes that a pre-planned exploratory analysis identified a sub-group with improved efficacy. That analysis was also supported by retrospective review of the JADETREE trial in China, which evaluated the drug in combination with capecitabine in second-line BTC patients. “The results from the study are disappointing,” said Carl Firth, Aslan’s chief executive officer. “They will, however, provide the scientific community with important insights into an aggressive and under-researched disease that presents a growing burden of care worldwide as prevalence arises.” Firth added, “I would like to extend our thanks to the patients, trial investigators and site personnel who participated in the study and to the Aslan team for their commitment to the development of varlitinib. Aslan remains focused on the promising molecules in its portfolio, including the ongoing study in atopic dermatitis of ASLAN004, our IL-13 receptor antibody which blocks signaling through IL-4 and IL-13. We look forward to the interim readout in early 2020.” Biliary tract cancer is a rare cancer of the bile tract, which is the tubes that transport bile produced by the liver into the small intestines. Two bile ducts originate from the liver and one from the gallbladder. They connect to form the common bile duct that connects to the small intestine. When food is digested, bile stored in the gall bladder is released and moves through the bile ducts into the small intestine. Biliary tract cancer can develop anywhere along the bile ducts. Another name for bile duct cancer is cholangiosarcoma. Additional names depend on where on the bile ducts the cancer is diagnosed. It is generally very difficult to treat. The company reported its third-quarter financials on October 29. In addition to the financial information, the company noted that it had presented late-breaking topline data from its Phase II trial in China of varlitinib and capecitabine in second-line BTC at the Chinese Society of Clinical Oncology meeting. In that trials, patients showed a response rate of 11%, including two complete responses, and median progression free survival was 2.7 months and OS was 5.8 months, which was still maturing. They pointed out that patients in the study seemed to present with a more aggressive disease with only 10% of patients responding to first-line gemcitabine-based treatment before enrollment. The company also presented new data from a Phase Ib open-label, dose escalation trial of varlitinib in combination with modified irinotecan and infusional 5-fluorouracil chemotherapy at the 2019 European Society for Medical Oncology Congress. The OS was 13% and the median PFS was 4.2 months.