Investment

Investment Strategy

Pharma Equity Group is an investment Company listed on the stock exchange that specializes in investing in the life science industry. It is Pharma Equity Groups’ ambition to focus on investments in life sciences companies who have clinical candidates in their portfolio, that are in an early stage of development (before phase II). The company’s investment strategy is designed to maximize returns while minimizing risk.

To identify potential investment opportunities, Pharma Equity Group follows a rigorous research and analysis process. This involves reviewing financial statements, studying industry trends, and speaking with industry experts to gain a deep understanding of the companies and sectors in which it is considering investing. Pharma Equity Group’s short-term investment strategy is to invest in life science companies in the Scandinavian market. The long-term investment strategy is to invest in companies worldwide.

To evaluate potential investments, Pharma Equity Group has developed a set of criteria that includes factors such as the strength of a company’s management team, the viability of its product or service, and its potential for growth. The company also considers the competitive landscape and market dynamics to ensure that the investment aligns with its overall strategy.

To diversify risk, Pharma Equity Group aims to create a well-balanced portfolio of investments across different sectors and companies. This can include investments in biotechnology and pharmaceuticals.

Overall, Pharma Equity Group’s investment strategy is designed to identify and invest in high-quality companies that have the potential to generate strong returns over the long term.

Reponex Pharmaceuticals A/S

Pharma Equity Group’s transaction with Reponex was approved in February 2023. Reponex Pharmaceuticals A/S is a clinical-stage biopharmaceutical company dedicated to the development of new, effective treatments for diseases that have a significant patient and social impact for which current therapy is lacking or in need of improvement. Reponex’s business model and drug development strategy consists of repositioning, rerouting, and recombining different established drugs and finding new use for it. Below you can read about the disease indication that currently are in the scope of Reponex Pharmaceuticals or follow the link below to enter the website of Reponex.

Bacterial Peritonitis

The aim of this project is to improve the treatment of incipient or established peritonitis (inflammation of the peritoneum) as a consequence of appendicitis or other intestinal perforations, thereby significantly reducing the length of hospitalization in favor of patients’ convenience and healthcare costs. Following a successful Phase 2 clinical acceptability and safety study, the second Phase 2 clinical trial in patients with a ruptured appendix has also been successfully completed with strong data. To read more about bacterial peritonitis click “read more” below.

Rationale for developing treatment for bacterial peritonitis

Peritonitis is an inflammation of the peritoneum, the epithelium that lines the abdominal cavity. The inflammation can occur either locally or diffusely in the abdomen. The severity of the disease is closely related to the extent of inflammation. Local inflammation as seen in uncomplicated appendicitis is an acute, reversible and less severe disease than diffuse peritonitis secondary to a perforation of the colon with faecal contamination throughout the abdomen. In the latter case, peritonitis can have long-term adverse consequences for the patient even with the best current treatment options.

Current practice for both local and diffuse peritonitis is surgical intervention (i.e. source control) supplemented with the systemic (intravenous) administration of antibiotics. In this new combination and new route of administration of drugs to treat peritonitis in combination with the current standard surgical intervention, the drugs are administered intraperitoneally, i.e. locally at the site of the disease. Thus, the highest concentration of the drugs is achieved at the site of the infection: in the abdominal cavity.

The combination of Reponex’s three main API’s has proven to introduce a better management of inflammation in the peritoneum. In a Phase II efficacy study of the new drug combination in peritonitfrom a ruptured appendix, the full data published in May 2020, showed outstanding efficacy with statistical significance and successfully achieved its primary endpoint by allowing the discharge of all patients within 2 to 21 hours (median 13 hours), on follow-up oral antibiotics. In comparison, it took from 67 to 169 hours (median 84 hours) before patients treated with intravenous antibiotics could leave the hospital. In addition, there were no complications in the patients receiving the drug combination, whereas two cases of intra-abdominal abscess (localised infection in the abdominal cavity) occurred among the control patients.

Incidence of primary indications: 1.7 million per year worldwide (586,000 per year EU+US)

Incidence of secondary indications: 855,000 per year worldwide (463,000 per year EU+US)

Wound Healing

Chronic ulcers in the form of venous leg ulcers and diabetic ulcers are a worldwide problem to the great inconvenience of affected patients.

There are several categories of non-healing wounds and ulcers, each of which has its own specialised treatment. These treatments include debridement of necrotic tissue, infection control and local wound care. However, non-healing wounds and ulcers have in common that they are typically caused by a deficiency in local blood supply, which fails to provide the nutritional means of keeping the cells involved in healing fully active. White blood cells (neutrophils) and macrophages fail in their housekeeping functions, and the macrophages fail to provide their normal stimulation of repair functions. Reponex has several programs running which are addressing various approaches to non-healing wounds. To read more about wound healing click “read more” below.

Rationale for developing treatments for wound healing

Chronic skin wounds are typically associated with diabetes, venous insufficiency, local pressure or ischemia. Common to these is a lack of local blood supply, which impairs the provision of the substances that are necessary to maintain full activity of the cells involved in the healing process. The white blood cells and macrophages do not perform their functions adequately, and the macrophages do not stimulate the healing processes as they normally would. By treating chronic wounds with Reponex main API, the cleansing functions of neutrophils and macrophages are restored, so that the macrophages can once again control the repair processes and accelerate healing.

Combination with other healing-promoting agents, RNX-022: other wound-healing promoting agents can be used in combination with Reponex main API to further accelerate the healing process. A second Reponex API promotes the synthesis and assembly of key extracellular matrix components such as interstitial collagens during wound healing. A third Reponex API amplifies the effects of intrinsic cytokines and growth factors involved in wound repair, e.g. basic fibroblast growth factor, by binding them and protecting them from degradation, so their effect on the wound healing process is prolonged. The three components of the combined treatment are expected to act additively or synergistically through their different mechanisms of action to thus accelerate wound healing.

Combination with antibiotics, RNX-023: Bacteria are present in all chronic wounds, but more than 16% of the wounds may in certain stages be more aggressively infected by pathogenic bacteria such as Staph. Aureus and/or P. aeruginosa. On its own, Reponex‘s main API can strengthen the local defense against bacterial infection by its action on neutrophils and macrophages, but the elimination of bacteria is accelerated if a high local concentration of an effective antibiotic is supplied as well. Reponex’s preferred antibiotic is particularly suitable since its broad spectrum covers most of the relevant pathogenic organisms, including methicillin-resistant S. aureus (MRSA), multidrug-resistant bacteria and many common strains of P. Aeruginosa. At the same time, it is remarkably non-toxic to the patient and the effector cells, neutrophils and macrophages, involved in healing. If bacterial culture from the wound detects special cases of organisms that are relatively insensitive to Reponex’s preferred antibiotic, combinations containing a second antibiotic may be employed. Some believe that the use of topical antibiotics for wound treatment may have unfavourable consequences in the form of the rapid development of bacterial resistance to the antibiotic that will make further treatment less effective and can generate yet another resistant strain that can be transmitted to other people. It is not expected to apply to the local use of Reponex’s preferred antibiotic, which will be applied at a high local concentration. If any bacterial resistance is developed, this will be due to the suppression of a biochemical mechanism in the bacterium itself, which leads to a weakening of the organism’s virulence and viability. The widespread use of antibiotics in other countries has not led to an increased prevalence of resistant strains in the population.

Prevalence of chronic leg ulcers: 47.9 million worldwide (13.9 million in EU+US)

Incidence of infected chronic leg ulcers: 7.2 million per year worldwide (1.5 million per year in EU+US)

Inflammatory Bowel Disease

Pouchitis

A special group of previously operated ulcerative colitis patients, having complete colon resection, suffer from a chronic, Crohn’s-like inflammation of the pouch constructed from the terminal ileum to allow normal defecation. This inflammatory condition is called “pouchitis”. Pouchitis causes great pain, very frequent toilet visits and often significantly reduced quality of life for the patients.

A clinical phase II trial on RNX-041 for the treatment of pouchitis is ongoing at Zealand University Hospital. The study will provide invaluable data for the design and execution of the subsequent placebo-controlled trial of RNX-041 for Crohn’s Disease.

Crohn’s Disease

Reponex seeks to improve on the current treatment of CD through the endoscopic intraintestinal administration of RNX-041 directly onto the affected areas. The application takes place via a spray catheter that can be directed to the target area through the endoscope used for localisation of the lesions. Applying Reponex main API locally from the intestinal lumen to the areas of inflamed and damaged mucosa has the potential to restore the impaired mucosal barrier and local macrophage function without provoking systemic inflammatory effects. At the same time, the local application of the antibiotics in RNX-041 can reduce the load of intestinal bacteria that trigger and sustain the abnormal inflammatory response. To read more about Crohn’s disease and pouchitis click “read more” below.

Rationale for developing treatment for Crohn’s Disease

The principle of the treatment is to supply RNX-041 locally to the inflamed areas of the intestinal mucosa from the intestinal lumen. The rationale is that this route of administration produces a favourable local effect of Reponex main API which acts to restore the disrupted mucosal barrier without provoking an augmented systemic inflammatory response (with an unfavourable activation of the destructive eosinophils and basophils). Similarly, the high local concentrations of the preferred Reponex antibiotics, which comprise a broad-spectrum antibiotics and an antibiotic against the B. fragilis-group, attenuate the pathogenic influences from the intestinal flora, especially from the Enterobacteriaceae and B. fragilis group of organisms that are suspected of maintaining the inflammatory condition. Reponex preferred antibiotic is considered to be a particularly suitable antibiotic for the aerobic bacteria, since it is active against many of the multidrug-resistant bacteria that occur in Crohn’s disease.

Prevalence of Crohn’s disease: 2.75 million worldwide (1.75 million in EU+US)

Incidence of pouchitis: 235,000 per year in EU+US

Colorectal Cancer

Rationale for developing RNX-051 for colorectal cancer

Fusobacterium is a genus of Gram-negative anaerobic bacteria, species of which, including F. nucleatum, are found in the oral cavity, where they play a role in periodontal disease. Genomic sequences of fusobacteria have been found to be enriched in colorectal cancer tumors, with a prominence of DNA sequences related to F. nucleatum. An overabundance of F. nucleatum RNA was also detected in such tumors. Fusobacteria target colorectal adenocarcinoma cells by means of their Fap2 lectin, which specifically binds to the D-galactose-β(1-3)-N-acetyl-D-galactosamine (Gal-GalNAc) residues of the surface carbohydrates of colorectal and certain other adenocarcinomas. Once in the tumor, the fusobacteria invade the cells and can enhance cellular proliferation, create a tumor-favourable inflammatory environment and protect the cancer cells against killing by natural killer cells and tumor-infiltrating T cells. F. nucleatum also promotes the resistance of colorectal cancers to chemotherapy, and because similar cellular mechanisms are involved, to radiotherapy. High fusobacterial abundance in colorectal cancer correlates with poor disease outcome. At the same time, there has been a call for antibacterial agents targeted specifically to fusobacteria to avoid the adverse effects of systemically administered broad-spectrum antibiotics.

Fusobacteria are highly sensitive to Reponex preffered antibiotic, which in turn is efficiently transported into intestinal mucosa cells to achieve bactericidal intracellular concentrations within a few minutes of being exposed to high extracellular concentrations. Local administration of the antibiotic via the bowel lumen, will result in a very high antibiotic concentration at the luminal surface of the tumor. The antibiotic penetrates into the tumor cells where the fusobacteria are located to achieve bactericidal concentrations very rapidly, while at the same time being less adequately absorbed into the blood than when given orally or systemically, so that any systemic adverse effects are reduced.

Quantitative polymerase chain reaction analysis of F. nucleatum DNA in the tumors demonstrates that the bacteria are concentrated in the superficial, luminal portion of the tumors. Therefore, antibacterial treatment by applying a high concentration of the antibiotic from the luminal side should be particularly effective in eliminating the bulk of the bacterial load.

Incidence of colorectal cancer: 1.9 million per year worldwide (586,000 per year EU+US)

New Drug Delivery Platform

In parallel with the development of RNX-041, it has been important for Reponex to develop a concept for administration of the active substances for the treatment of intestinal lesions in the form of an oral drug, so that patients can receive treatment daily comfortably and without significant inconvenience.

Reponex has been developing a new concept and technology that entails the targeting of the active ingredients in RNX-041 and possibly other biological agents directly to the intestinal lesions, by binding the agents to known and approved substances that in themselves bind selectively to the lesions and prolong the contact of the biological agents with the ulcer bed. RNX-042 is to be administrated orally by a gel forming substance protecting the biological agents until reaching the terminal ileum where the gel dissolves and releases the active ingredients. To read more about new drug delivery platform click “read more” below.

Providing local intraluminal intestinal treatments by means of oral formulation.

Two main concepts are being studied that can be used individually or in combination to target the drugs to the intestinal lesions in Crohn’s Disease:

Adsorption (surface binding) of the fragile but important active protein in Reponex’s medicinal drug, which builds the integrity of the intestinal mucosa, into a known ulcer-treating particle product that binds the protein, protects it from the breakdown of stomach acid and digestive enzymes, binds to defects in intestinal mucosa and enhances the action of the adsorbed protein.

Dissolve the active substances in a small amount of a thin liquid containing substances which form a soft gel lump when the liquid is swallowed and comes into contact with the stomach acid. The drugs remain significantly inside the gel, thereby protecting against the full effect of stomach acid and digestive enzymes. The gel is transported down the intestine, but is broken down again in the transition from the small intestine to the large intestine, thus triggering the drugs. This could prove to be suitable for the treatment of Crohn’s lesions in the terminal small intestine and / or the subsequent part of the large intestine. Preliminary studies so far indicate a satisfactory incorporation of the API into the gel when it is formed in contact with simulated gastric acid.

Reponex attaches great importance to the development of these possible oral treatments for intestinal lesions, as thy are expected to enable the performance of what is actually a local treatment that would most often require invasive endoscopy, as a convenient oral treatment for daily use.

Through the development work with RNX-042, this dynamic gel concept has proven to be particularly suitable for the delivery of particle preparations further down the intestine, including probiotic bacteria, which is also specified in the filed patent application.

Reponex’s innovative drug administration platform opens up completely new possibilities for local targeted treatments in the gut, which go far beyond Reponex’s current development program.

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