Novel antibiotic development expertise apparent
Dr Brian White
19 May 2021
The announcement this morning of an award of up to $2.7m from CARB-X for the development of a novel antibiotic targeting Gram-negative bacteria is testament to the growing anti-infectives expertise within Basilea, and the increasing unmet medical need to develop novel antibiotics against emerging resistance. While the future of Basilea is increasingly inextricably linked to its nascent oncology programmes, it currently receives a significant royalty stream from its anti-infectives franchise - principally the anti-fungal Cresemba as well as the antibiotic Zevtera (ex US). Additionally, ceftobiprole continues to progress through Phase 3 development in the US in the Staph aureus bacteraemia indication (TARGET) with positive results already received from the severe skin infection study (ERADICATE), largely funded by BARDA.
Resistant Gram-negative infections particularly worrying
Gram-negative infections are increasingly problematic with few treatment options available. The ESKAPE pathogen group has been highlighted as particularly at risk given their propensity to develop resistance to commonly used antibiotics. Many ESKAPE pathogens including multi-drug resistant Pseudomonas aeruginosa, carbapenem-resistant Enterobacterales and Acinetobacter baumannii have been highlighted as being of particular concern from august organisations including the WHO and the US Centers for Disease Control and for which new antibiotics are urgently required.
Novel approaches required
The approach followed by Basilea involves targeting the development of DXR inhibitors - the second enzyme in the methylerythritol phosphate (MEP) pathway in bacterial isoprenoid biosynthesis. Isoprenoids are vital for cell survival and are involved in a wide variety of cellular functions in animals, plants and bacteria. In bacteria they are involved in cell wall synthesis (peptidoglycans) as well as functioning of the electron transport chain. In animals, isoprenoid biosynthesis proceeds exclusively via the mevalonate pathway, while the majority of bacteria use the MEP pathway. The absence of the MEP pathway in humans makes enzymes involved in this pathway attractive targets for novel antibiotic development. Although each of the seven MEP enzymes is a potential target, many have presented challenges with respect to inhibitor design. DXR appears to be a particularly promising target as the first committed step in MEP biosynthesis and given that it is encoded by a single gene product it has a lower risk of developing intrinsic resistance. These are early days, but we look forward to future developments as the programme progresses.
Calvine Partners LLP is authorised and regulated by the Financial Conduct Authority in respect of UK investment advisory and arranging activities.
This publication has been commissioned and paid for by Basilea Pharmaceutica and as defined by the FCA is not independent research. This report is considered to be a marketing communication under FCA rules, and it has not been prepared under the laws and requirements established to promote the independence of investment research, and it is not subject to any prohibition on dealing ahead of the dissemination of investment research. The information provided is widely available to the public.
This report in the United Kingdom is directed at investment professionals, certified high net worth individuals, high net worth entities, self-certified sophisticated investors, eligible counterparties as defined by Financial Services and Markets Act 2000 (Financial Promotion) Order 2000. The report may also be distributed and made available to persons to whom Calvine Partners is lawfully permitted. This publication is not intended for use by any individual or entity in any jurisdiction or country where that use would breach law or regulations, or which would subject Calvine Partners or its affiliates to any registration requirement within such jurisdiction or country.
Calvine Partners may provide, or seek to provide, services to other companies mentioned in this report. Partners, employees, or related parties thereof may hold positions in the companies mentioned in the report subject to Calvine Partners’ personal account dealing rules.
Calvine Partners has only used publicly available information believed to be reliable at the time of this publication and made best efforts to ensure that the facts and opinions stated are fair, accurate, timely and complete at the publication date. However, Calvine Partners provides no guarantee concerning the accuracy or completeness of the report or the information or opinions within. This publication is not intended to be an investment recommendation, personal or otherwise, and it is not intended to be advice and should not be treated in any way as such. Any valuation estimates, such as those derived from a discounted cash flow, price multiple, or peer group comparison, do not represent estimates or forecasts of a future company share price. In no circumstances should the report be relied on or acted upon by non-qualified individuals. Personal or otherwise, it is not intended to be advice and should not be relied on in any way as such.
Forward-looking statements, information, estimates and assumptions contained in this report are not yet known, and uncertainties may cause the actual results, performance or achievements to be significantly different from expectations.
This report does not constitute an offer, invitation or inducement to engage in a purchase or sale of any securities in the companies mention. The information provided is for educational purposes only and this publication should not be relied upon when making any investment decision or entering any commercial contract. Past performance of any security mentioned is not a reliable indicator of future results and readers should seek appropriate, independent advice before acting on any of the information contained herein. This report should not be considered as investment advice, and Calvine Partners will not be liable for any losses, costs or damages arising from the use of this report. The information provided in this report should not be considered in any circumstances as personalised advice.
Calvine Partners LLP, its affiliates, officers or employees, do not accept any liability or responsibility with regard to the information in this publication. None of the information or opinions in this publication has been independently verified. Information and opinions are subject to change after the publication of this report, possibly rendering them inaccurate and/or incomplete.
Any unauthorised copying, alteration, distribution, transmission, performance, or display, of this report, is prohibited.