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Research led by Curve CSO Professor Ali Tavassoli's laboratory at University of Southampton Landmark paper on dual HIF-1 and HIF-2 inhibitor that works by inhibiting the interaction of both HIF-1α and HIF-2α with HIF-1β SOUTHAMPTON, England, March 26, 2024 /PRNewswire/ -- Curve Therapeutics ("Curve" or the "Company"), a private biotechnology company pioneering a revolutionary intracellular screening platform addressing complex and challenging disease targets, today announces the publication of an article in the Journal of the American Chemical Society (JACS). The paper entitled 'Identification and Development of Cyclic Peptide Inhibitors of Hypoxia Inducible Factors (HIF) 1 and 2 That Disrupt Hypoxia-Related Signalling in Cancer Cells' can be viewed here.1 Curve's Chief Scientific Officer, Professor Ali Tavassoli, co-authored the article and leads the academic group at the University of Southampton where the work was undertaken. Professor Ali Tavassoli, Chief Scientific Officer of Curve Therapeutics, said: "It is well recognised that HIF plays a key role in the survival and growth of solid tumours. The compounds we report in this paper inhibit the protein-protein interaction of the two subunits that form the HIF transcription factor. We show that these compounds prevent the hypoxia-induced activity of this transcription factor, stopping hypoxia-response in cell-based assays. This paper underlines the promising therapeutic potential of dual HIF inhibition as an approach for the treatment of a variety of cancers." Curve Therapeutics is a leader in the discovery of innovative therapeutics to address disease targets which are difficult to target using conventional drug discovery methods. Through the utilisation of its world leading Microcyle® discovery platform, Curve can screen directly inside mammalian cells, allowing for the identification of biologically active library members within an intracellular environment where both the library and the target are present in their native conformations. Curve is developing a non-peptidic, small-molecule dual inhibitor of HIF-1 and HIF-2 with first-in-class potential. This is the first report of a dual HIF-1 and HIF-2 inhibitor which functions by inhibiting the interaction of both HIF-1α and HIF-2α with HIF-1β. The Microcycles discovered by Prof. Tavassoli were identified using his SICLOPPS screening platform and show good cellular activity. Patents and patent applications describing these HIF inhibitory Microcycles are exclusively licensed to Curve. About Curve Therapeutics Curve Therapeutics is a private biotechnology company pioneering a revolutionary intracellular screening platform to enable the discovery of innovative therapeutics that address complex and challenging disease targets with the potential to transform the lives of patients. Curve originated from world-leading Microcycle® research conducted by Professor Tavassoli's group in the Department of Chemistry at the University of Southampton, UK. Curve is backed by blue chip investors including Advent Life Sciences, Epidarex Capital, Pfizer Ventures, Columbus Venture Partners and British Patient Capital. Curve has a US$1.7bn global research collaboration with MSD the trade name of Merck & Co., Inc., Kenilworth, NJ USA, to discover and validate modulators of up to five therapeutic targets using its Microcycle® technology, initially for oncology and neurology indications. For more information visit: . About Curve's Microcycle® platform Curve has developed an IP-protected, mammalian cell platform technology for functional screening and enrichment of diverse hexameric cyclic peptide Microcycle® libraries to identify those library members that have the desired biological activity against a therapeutic target. Curve's platform allows direct screening for biologically active library members inside mammalian cells and facilitates small molecule hit-to-lead programmes. A key advantage of the technology is that both the library and the target are present in all of their native conformations within a cell. Uniquely, the compact size and rigid structure of Microcycles® enables the design of non-peptide small molecule leads. The platform can be used for a wide range of therapeutically relevant targets, including protein-protein and protein-DNA interactions and has been used by Curve to develop a pipeline of cancer programmes against targets including a dual HIF-1/HIF-2 inhibitor and an inhibitor of ATIC homodimerization. [1] Andrew T. Ball, Soran Mohammed, Cyrielle Doigneaux, Reece M. Gardner, James W. Easton, Steven Turner, Jonathan W. Essex, Garry Pairaudeau, Ali Tavassoli, Identification and Development of Cyclic Peptide Inhibitors of Hypoxia Inducible Factors 1 and 2 That Disrupt Hypoxia-Response Signaling in Cancer Cells, Journal of the American Chemical Society (19 March 2024) DOI: 10.1021/jacs.3c10508 SOURCE Curve Therapeutics

With a drug-development deal already in place with Merck & Co., Curve Therapeutics has now added backing from the venture arm of Pfizer to fund its internal pipeline of cancer therapies against challenging targets.CEO Simon Kerry said the financing “will enable us to expand our team, progress our lead assets into the clinic and to expand our drug discovery platform.” Pfizer Ventures led the £40.5 million ($51 million) Series A financing, which included new investors British Patient Capital and Columbus Venture Partners, as well as former backers Advent Life Sciences and Epidarex Capital.Curve is hoping that its Microcycle platform will enable it to discover biologically active molecules against targets that have been difficult to address using conventional drug discovery methods. The company’s pipeline includes a dual-inhibitor of HIF-1 and HIF-2, as well as an inhibitor of ATIC dimerisation that targets an important vulnerability in multiple cancers.Marie-Claire Peakman, partner at Pfizer Ventures, remarked “Curve's platform provides an exciting new approach designed to tackle tough, high priority targets which have been difficult to progress in the past.” The platform allows functional screening and enrichment of Microcycle libraries within the cytoplasm of mammalian cells to identify compounds that have a desired biological activity against a therapeutic target. Curve noted that the compact size of Microcycles enables their transformation to non-peptide small molecules for lead optimisation and development.The deal signed with Merck in 2022 covers modulators of up to five therapeutic targets, initially for oncology and neurology indications, and is potentially worth up to $1.7 billion to Curve. As part of the agreement, the company is undertaking optimisation using its Microcycle technology.

Series A financing led by Pfizer Ventures with new investors Columbus Venture Partners and British Patient Capital which join founding investor Advent Life Sciences and seed investor Epidarex Capital Goal to advance proprietary discovery platform and progress pipeline of assets addressing challenging cancer targets into the clinic SOUTHAMPTON, England, Feb. 27, 2024 /PRNewswire/ -- Curve Therapeutics ("Curve" or the "Company"), a private biotechnology company pioneering a revolutionary intracellular screening platform addressing complex and challenging disease targets, today announces the close of its successful £40.5 million Series A financing. Pfizer Ventures led the round with participation from Columbus Venture Partners and British Patient Capital, which join founding investor Advent Life Sciences and co-lead from the seed round, Epidarex Capital. Curve's powerful Microcycle® platform enables the direct discovery of biologically active molecules against targets that have been difficult to address using conventional drug discovery methods. Curve has built a discovery pipeline of assets including a first-in-class dual-inhibitor of HIF-1 and HIF-2 that addresses survival mechanisms in more than half of solid tumours, and a first-in-class inhibitor of ATIC dimerization that targets an important vulnerability in multiple cancers. The financing will enable the Company to progress development of these assets rapidly towards clinical development and to expand the discovery platform beyond challenging and complex intracellular protein targets. Simon Kerry, PhD, MBA, Chief Executive Officer of Curve Therapeutics, said: "This financing will enable us to expand our team, progress our lead assets into the clinic and to expand our drug discovery platform. We welcome our new investors alongside our existing strong syndicate and look forward to working together to take Curve to its next stage of growth." Professor Ali Tavassoli, Chief Scientific Officer of Curve Therapeutics, added: "Curve's Microcycle platform is a powerful tool for drug discovery, enabling an unparalleled advantage in the discovery of functional hits and leads. We look forward to maximising the potential of our platform to further develop a rich pipeline of programmes with the potential to treat unmet clinical needs in a diverse range of diseases, including cancer." Dr. Marie-Claire Peakman, Partner at Pfizer Ventures, commented: "We are delighted to have led this financing and to work with great co-investors and leadership team. Curve's platform provides an exciting new approach designed to tackle tough, high priority targets which have been difficult to progress in the past. We are eager for the Company to progress the platform with the goal of identifying new therapeutics for challenging diseases." Curve's platform allows functional screening and enrichment of highly diverse, gene-encoded, Microcycle libraries within the cytoplasm of mammalian cells to identify library members that have a desired biological activity against a therapeutic target. Importantly, the compact size of Microcycles enables their transformation to non-peptide small molecules for lead optimisation and development, an unparalleled advantage compared to other cyclic peptide technologies. Curve occupies state of the art laboratories at the Southampton Science Park, a move prompted by the expansion of the Company's research team which included the recent appointments of Dr Monika Ermann as Vice President of Drug Discovery, and Dr Sally Price as Vice President of Biology. With four regional Universities and pioneering medical institutions such as the Centre for Cancer Immunology in Southampton, Hampshire is an attractive location for life science companies, and just an hour from key biotech centres in Oxford and London. About Curve Therapeutics Curve Therapeutics is a private biotechnology company pioneering a revolutionary intracellular screening platform to enable the discovery of innovative therapeutics that address complex and challenging disease targets with the potential to transform the lives of patients. Curve originated from world-leading Microcycle® research conducted by Professor Tavassoli's group in the Department of Chemistry at the University of Southampton, UK. Curve is backed by blue chip investors including Advent Life Sciences, Epidarex Capital, Pfizer Ventures, Columbus Venture Partners and British Patient Capital. Curve has a US$1.7bn global research collaboration with MSD the trade name of Merck & Co., Inc., Kenilworth, NJ USA, to discover and validate modulators of up to five therapeutic targets using its Microcycle® technology, initially for oncology and neurology indications. For more information visit: About Curve's Microcycle® platform Curve has developed an IP-protected, mammalian cell platform technology for functional screening and enrichment of diverse hexameric cyclic peptide Microcycle® libraries to identify those library members that have the desired biological activity against a therapeutic target. Curve's platform allows direct screening for biologically active library members inside mammalian cells and facilitates small molecule hit-to-lead programmes. A key advantage of the technology is that both the library and the target are present in all of their native conformations within a cell. Uniquely, the compact size and rigid structure of Microcycles® enables the design of non-peptide small molecule leads. The platform can be used for a wide range of therapeutically relevant targets, including protein-protein and protein-DNA interactions and has been used by Curve to develop a pipeline of cancer programmes against targets including a dual HIF-1/HIF-2 inhibitor and an inhibitor of ATIC homodimerization. SOURCE Curve Therapeutics